Dietary habits and metabolic syndrome in middle-aged Europeans.
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Lipgene – Diet, genomics, and the metabolic syndrome: 1 an integrated nutrition, agro-food, social and economic analysis Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Lipgene
2 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Contents Lipgene: A Ground-breaking Project to Tackle the Burden of the Metabolic Syndrome Foreword from Prof. Michael Gibney, Principle Investigator of the Lipgene Project 1 Programme for the Final Conference 2 Session 1: Lipids, Genes and the Metabolic Syndrome 3 Session 2: Optimising Fats in the Food Chain 5 Session 3: What do European Consumers Think About the Metabolic Syndrome, Functional and Genetically Modifi ed Foods? 7 Session 4: Impact of the Project 8 Posters from the Lipgene Consortium 9 Background to the Project 1.0 Introduction 36 2.0 The Metabolic Syndrome 37 3.0 Dietary Fat 39 3.1 Health Effects of Dietary Fat 40 3.2 Fats in the Human Food Chain 41 4.0 The Association between Dietary Fat and the Metabolic Syndrome 42 5.0 Foods of the Future – Social and Economic Aspects 43 6.0 Genetics and the Metabolic Syndrome 44 7.0 Findings from the Project (2004–2009) 45 7.1 Human Nutrition Studies 47 7.2 Plant Biotechnology 49 7.3 Animal Nutrition 50 7.4 Economics 52 7.5 Consumer Understanding and Awareness 53 7.6 Dissemination 54 7.7 Demonstration 55 References 56 Appendix 1: Q&A: Genetically Modifi ed Foods 58 Appendix 2: Q&A: Obesity in Europe – A fat price to pay? 60 Appendix 3: Lipgene Publications 63 Appendix 4: Lipgene Partners 74 Acknowledgment: This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944) (http://www.ucd.ie/Lipgene)
Lipgene – Diet, genomics, and the metabolic syndrome: 1 an integrated nutrition, agro-food, social and economic analysis Foreword from Prof. Michael Gibney The metabolic syndrome encompasses a series of conditions which are frequently seen together: abdominal obesity, hypertension, high blood lipids and insulin resistance. According to the World Health Organization, there will be 700 million adults with obesity by 2015. Clearly, prevention is the fi rst option in combating the metabolic syndrome and, of course, curing the condition through sustained weight loss and physical activity is a second, but much less successful option. There is a third option which was the very centre of the Lipgene project: minimising some of the adverse effects through dietary change. When the Lipgene consortium was being assembled back in 2003, limited human data and extensive data from animal studies suggested a strong effect of dietary fat levels and composition on one of the main elements of the metabolic syndrome, insulin resistance. Thus, one of the major tasks for Lipgene was to carry out the largest ever human intervention study of diet and the metabolic syndrome: 480 subjects followed for 12 weeks in 8 EU cities. The human genome sequence was released when Lipgene was being formed and we drew on a large French cohort of over 13,000 subjects who were followed for 8 years. We identifi ed almost 877 of these who were healthy at the outset and remained healthy, and they were matched with an equal number of those who went on to develop the metabolic syndrome. This would allow us study how genes interact with nutrients to explain why some people do and others do not develop the metabolic syndrome. Looking backwards into the food chain, we then asked the question: “can new technologies allow us to modify the fatty acids in the food chain?” We looked at new approaches to dairy and poultry nutrition and also how genetic engineering could enhance oil seed crops with algae genes to make long chain omega 3 fatty acids. But Lipgene also looked forward to consider possible outcomes and thus we studied the economics of changing the dietary fat supply and also the perception of consumers to the problem of the metabolic syndrome, to genetic testing to optimise nutrition and to their attitudes to new technologies. I would like to thank all of those who worked on the Lipgene project and the staff of Directorate General Research for making this project so successful. Prof. Michael Gibney Principal Investigator Institute of Food and Health University College Dublin
2 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Programme for the Final Conference Held at the University College Dublin, Ireland on the 5th December 2008 0900 – 0915 Registration, Coffee and Posters 0915 – 0930 Welcome and Introduction, Prof. Christine Williams, University of Reading, UK Opening of the Meeting, Dr. Patrick Cunningham, Chief Government Scientifi c Advisor, Ireland Chair: Prof. Mike Gibney, University College Dublin, Ireland Session 1: Lipids, Genes and the Metabolic Syndrome 0930 – 1000 During this session, Prof. Helen Roche from University College Dublin, Ireland & Prof. Denis Lairon, INSERM France will outline the fi ndings from Lipgene in relation to common genetic variations, how they interact with diet and predispose aspects of the metabolic syndrome. 1000 – 1010 Questions Session 2: Optimising Fats in the Food Chain 1010 – 1030 Prof. Ian Givens from the University of Reading, UK will discuss efforts by Lipgene to use novel animal nutrition to modify the fat content of diet. 1030 – 1040 Questions 1040 – 1100 Dr. Thorsten Zank, BASF Plant Science, Germany will present the activities and outcome from Lipgene to use novel genetic methods to deliver a sustainable supply of polyunsaturated fatty acids from crop plants. 1100 – 1110 Questions 1110 – 1140 Coffee, Posters and Prototype Tasting Session 3: What do European Consumers Think About the Metabolic Syndrome, Functional and Genetically Modifi ed Foods? 1140 – 1200 Research from Lipgene assessing European opinion and attitudes towards genetic screening of people’s diets (personalised nutrition) and the use of genetically modifi ed foods will be presented by Prof. Maria Daniel Vaz de Almeida, University of Porto, Portugal and Dr. Barbara Stewart-Knox, University of Ulster, UK. 1200 – 1210 Questions Session 4: Impact of the project 1210 – 1240 Prof. Ian Givens, University of Reading, UK will discuss how novel approaches to modify the fat content of foods can impact on cardiovascular health and the economic implications of such innovations in Europe. 1240 – 1250 Questions 1250 – 1305 Panel Discussion 1310 – 1315 Conclusion and Close 1315 – 1415 Lunch and Posters
Lipgene – Diet, genomics, and the metabolic syndrome: 3 an integrated nutrition, agro-food, social and economic analysis Session 1: Lipids, Genes and the Metabolic Syndrome Prof. Helen Roche, University College Dublin, Ireland Speaker Biography Helen Roche was recently appointed Associate Professor of Nutrigenomics at the Conway Institute, University College Dublin, Ireland. She is also a SFI Principal Investigator within the context of Molecular Nutrition. Prior to that as Wellcome Trust Fellow & Senior Lecturer in Molecular Nutrition at Trinity College Dublin, Dr. Roche established the fi rst Nutrigenomics research group in Ireland, at the Institute of Molecular Medicine at Trinity College Dublin. Prof. Roche has at least 50 publications cited in Medline. Recent work published in Diabetes (Impact Factor 9) presented novel fi ndings with respect to infl ammation in adipose tissue, insulin resistance and nutrient regulation of gene expression. Other top nutrition journals Prof. Roche’s published work appears in include FASEB Journal, Journal of Immunology, American Journal of Clinical Nutrition & British Journal of Nutrition. Prof. Denis Lairon, INSERM, France Speaker Biography Prof. Lairon completed a PhD in biochemistry in 1979. Following this he has undertaken roles including Research Director at Inserm (National Institute of Health and Medical Research) in 1999, Director of the Joint Research Unit 476 Inserm/1260 Inra/Université de la Méditerranée “Human Nutrition and lipids: bioavailability, metabolism and regulations” at Marseille, France from 1998-2007, and has been Vice-President (1994; 2005) and President (1995-98) of the French Nutrition Society. He is also president of the Federation of European Nutrition Societies (FENS), 2007-2011. As well as working on the Lipgene project, he is involved in two further European Projects, 3 COST actions, and NoE-NUGO. Abstract The metabolic syndrome is a very common disease associated with an increased risk of type 2 diabetes mellitus and cardiovascular disease. Diet and genetic susceptibility play a major role in the development and progression of the condition. In terms of dietary factors there is strong evidence to suggest that dietary fatty acid composition affects insulin sensitivity. Genetic background can interact with habitual dietary fat composition, thereby affecting predisposition to the metabolic syndrome and may also determine an individual’s responsiveness to altered dietary fat intake. Therefore Lipgene Human Nutrition Programme addressed this hypothesis in two ways. Firstly the Lipgene prospective case-control study determined the interaction between dietary fat composition and the development of the metabolic syndrome. Secondly the Lipgene Dietary Intervention Study determined the relative effi cacy of reducing dietary saturated fatty acid (SFA) consumption, by altering quality and reducing the quantity of dietary fat, on metabolic risk factors of the metabolic syndrome.
4 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis The Lipgene prospective case-control study used the pre-existing SUVIMAX cohort (13,500 subjects followed 7y) to retrospectively select a Lipgene cohort (877 cases with metabolic syndrome and 877 matched controls). Genetic characteristics (182 candidate genes and 806 single nucleotide polymorphisms (SNPs)), baseline dietary composition focusing on fat intake and baseline plasma fatty acid composition (a biomarker of fat intake) were determined to study the interaction between dietary fat composition and genes associated with the risk of the metabolic syndrome in the development of the metabolic syndrome. As expected the phenotypes used to defi ne the metabolic syndrome, including BMI, waist circumference, hypertension, elevated triacyl glyceride concentrations and low highdensity lipoprotein levels were signifi cantly different between metabolic syndrome cases and controls. Metabolic syndrome cases had signifi cantly lower plasma total omega-6 and omega-3 polyunsaturated fatty acids (PUFA) but higher SFA (C14:0 & C16:0), compared to controls. Cases had lower education levels, more likely to be smokers and less physically active. Baseline dietary energy intake was higher in metabolic syndrome cases, whilst energy intake from fat was not different between groups. PCA analysis showed that plasma SFA and omega-6 PUFA were associated with increased metabolic syndrome risk, but long chain omega-3 PUFA were linked to reduced metabolic syndrome risk. Genetic markers linked with the development of the metabolic syndrome identifi ed 7 single nucleotide polymorphisms in 6 genes, related to lipid metabolism and infl ammation different between metabolic syndrome cases and controls. On-going analysis is defi ning interactions between apo B, C3 and other genes which are showing promising diet-gene interactions. In conclusion, this work showed that dietary fatty acids, and especially plasma fatty acids, are involved in the development of the metabolic syndrome while few gene polymorphisms can make subjects more or less susceptible. In the Lipgene Human Intervention Study 417 free-living subjects with the metabolic syndrome received one of four dietary treatments for 12 weeks: (1) High-fat (38% energy) SFA-rich diet (HFSFA); (2) High-fat (38% energy), monounsaturated fatty acid (MUFA)-rich diet (HFMUFA); (3) Low-fat (28% energy), high-complex carbohydrate diet (LFHCC) and (4) Low-fat (28% energy), high-complex carbohydrate diet, with 1.24 g/d LC n-3 PUFA (LFn-3PUFA). Detailed metabolic (IVGTT, cytokines, adhesion molecules, coagulation factors and isoprostane analysis) with additional postprandial lipoprotein metabolism, skeletal muscle cellular fatty acid uptake and glucose disposal stable isotope studies and cellular mitochondrial status assessment preand post-intervention combined with genetic analysis revealed a vast amount of interesting data. Key results with respect to the effect of dietary fat modifi cation on metabolic risk factors associated with the metabolic syndrome are presented here. Dietary fat modifi cation had no signifi cant effect on insulin sensitivity (SI) or insulin resistance (HOMA-IR) in the whole cohort. When habitual fat intake pre-intervention (highor low-fat intake > or < the median 36% of energy from fat) was taken into account SI was signifi cantly lower following the HSFA diet in subjects, particularly females, with a habitual low-fat intake pre-intervention. Insulin resistance (HOMA-IR) was reduced in females following the HMUFA diet. Plasma TAG, TRL and NEFA concentrations improved following the LFHCC omega-3 PUFA diet particularly in males. HDL-c concentrations were augmented by both high-fat diets. Dietary SFA modifi cation had no effect on markers of infl ammation, coagulation or oxidative stress. Postprandial lipid metabolism and skeletal muscle fatty acid handling was most affected by the LFHCC omega-3 PUFA diet. Interestingly infl ammatory genes were linked to responsiveness to dietary therapy. In conclusion therapeutic dietary therapy for the metabolic syndrome may require a ‘personalised nutrition’ approach, wherein habitual fat intake and genetic profi le may determine responsiveness to specifi c dietary fatty acid interventions.
Lipgene – Diet, genomics, and the metabolic syndrome: 5 an integrated nutrition, agro-food, social and economic analysis Session 2: Optimising Fats in the Food Chain Prof. Ian Givens, University of Reading, UK Speaker Biography Prof. Ian Givens is currently Director of Animal Sciences Research Group (incorporating the Nutritional Sciences Research Unit, Biomathematics and the Centre for Dairy Research) in the University and joint leader of the University’s Food Chain and Health Research Theme. He graduated from the University of Newcastle-upon-Tyne with a 1st class Honours Degree in Biochemistry and Nutrition with a subsequent PhD from the same university. Prof. Givens has worked for the Ministry of Agriculture, Fisheries and Food as a Nutritional Chemist and for ADAS as head of The Nutritional Sciences Research Unit. He has a particular interest in the relationship between the nutrition of animals, the composition of animal derived foods and their impact on human nutrition and chronic disease. Abstract In spite of the recognised benefi ts of reducing saturated fatty acid (SFA) intake few parts of the European Union (EU) meet recognised targets. Milk and dairy products represent the single largest source of dietary SFA in most countries, yet epidemiological evidence indicates that milk has cardioprotective properties such that simply reducing consumption of dairy foods to meet SFA targets may not be a sound public health approach. The animal nutrition workpackage has explored the options for replacing some of the SFA in milk fat with cis-monounsaturated fatty acids (MUFA) through alteration of the diet of the dairy cow and the evidence that such changes can improve the indicators for cardiovascular disease in general in the consumer. In addition the benefi cial effects of long chain (LC) (carbon chain ≥20) omega-3 polyunsaturated fatty acids are well documented but recent evidence indicates that few people achieve the UK daily recommended intake for adults of 450 mg of EPA + DHA per day. In many parts of Europe the daily intake of EPA + DHA by adults and especially young people is less than 100 mg per day, since many never eat oily fi sh. Poultry meat contributes small but worthwhile amounts of EPA + DHA and studies to enrich the EPA + DHA content of animal-derived foods will be described and how this would impact on habitual intake. Dr. Thorsten Zank, BASF Plant Science, Germany Speaker Biography Dr. Thorsten Zank studied Biology (Molecular Biology, Biochemistry & Plant Physiology) at the University of Hamburg, before going on to complete a PhD on the isolation and characterisation of genes involved in the biosynthesis of long chain polyunsatured fatty acids in the group of Prof. Dr. Ernst Heinz at the University of Hamburg in cooperation with BASF Plant Science (after 1 year post-doc). Since 2003 he has been working as a research scientist and innovation manager at BASF Plant Science, and has 10 years of expertise in the fi eld of plant lipid biochemistry and molecular biology.
6 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Abstract Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) are widely accepted to have a positive effect on the prevention of diseases associated with the metabolic syndrome. The major source of these omega-3 LC-PUFAs is currently fi sh, while the primary producers of these omega-3 LC-PUFAs are marine microorganisms that form the basis of the marine food chain. However, since the demand for LC-PUFAs is increasing, fi sh stocks are decreasing drastically due to overfi shing. Additionally, as a result of environmental pollution, fi sh is more and more enriched with harmful substances like heavy metals, dioxin and softeners. It was therefore the goal of this joint effort between the University of York, Rothamsted Research and BASF Plant Science to develop an alternative, sustainable, safe and cheap source for LC-PUFAs for human nutrition. During the last fi ve years, the partners aimed to modify the composition of vegetable oils—the traditional oil source for human consumption—towards substantial proportions of LCPUFAs by novel genetic methods. The main advantages of LC-PUFAs produced in oilseed crops, such as rapeseed, compared to fi sh oil are (i) lower odour and sensory problems, (ii) less contamination in source oil, (iii) healthy vegetable fatty acids as by-products, in particular oleic acid, and (iv) plants as a sustainable and cheap source for fatty acids. In a fi rst step, genes have been identifi ed from microorganisms (e.g. the alga Thallasiosira pseudonana) and transferred to rapeseed for seed specifi c expression. These transgenic plants have been used for detailed biochemical characterisation by applying various analytical tools developed during the course of the Lipgene project. These tools helped to get a comprehensive understanding of LC-PUFA biosynthesis within the seeds, and to identify bottlenecks limiting the accumulation of the desired LC-PUFAs to higher proportions. Several strategies aiming to circumvent these bottlenecks have been conducted, and the knowledge gained resulted in the successful genetic optimisation of oilseed rape towards the accumulation of signifi cant proportion of LC-PUFAs in their seed oil.
Lipgene – Diet, genomics, and the metabolic syndrome: 7 an integrated nutrition, agro-food, social and economic analysis Session 3: What do European Consumers Think About the Metabolic Syndrome, Functional and Genetically Modifi ed Foods? Prof. Maria Daniel Vaz de Almeida, University of Porto, Portugal Speaker Biography Professor Maria Daniel Vaz de Almeida, BSc (Human Nutrition), PhD (Nutrition), is a nutritionist, Professor of Public Health Nutrition / Community Nutrition at the Faculty of Nutrition and Food Sciences of Porto University. Currently, she is the national leader of several European funded Projects, namely: (1) Eating Out: Habits, Determinants, and Recommendations for Consumers and the European Catering Sector – HECTOR (2006-2009) (2) Promotion of vegetable and fruit consumption of school children – PRO GREENS (2008-2011) and (3) Expansion and update of existing nutrition monitoring systems – ANEMOS (2008-2010). In Lipgene she was the workpackage leader of the consumer science research. Together with Dr. Barbara Stewart-Knox she coordinated the qualitative and quantitative consumer research of the project. Her main research interests are determinants of food consumption, consumer attitudes and food intake. Dr. Barbara Stewart-Knox, University of Ulster, UK Speaker Biography Barbara is currently a Senior Lecturer based within the Northern Ireland Centre for Food and Health (NICHE) at the University of Ulster, Coleraine. NICHE is an interdisciplinary research unit that received a fi ve-star rating in the two previous research assessment exercises (RAE). Interests are broad within consumer health, diet and lifestyle. Principle investigator of several externally funded projects, Barbara has published 60+ papers in peer reviewed academic journals. Abstract Negative consumer opinion poses a potential barrier to the application of intervention to prevent and treat metabolic syndrome. These analyses have explored uptake and attitudes toward functional foods, GM foods and personalised nutrition among the European public. An omnibus opinion survey of a representative sample aged 14-55+ years (n=5967) took place in France, Italy, Great Britain (GB), Portugal, Poland and Germany during June 2005 as part of the Lipgene project. Individuals who are aware they have health problems associated with metabolic syndrome or who perceive themselves at risk of developing metabolic syndrome appear particularly favourable toward functional genetically modifi ed (GM) food and nutrigenomic intervention. The fi ndings are encouraging for the future uptake of GM food provided they deliver health and other tangible benefi ts and for the application of personalised nutrition provided that policies are put in place to address public concern about how genetic information is used and held.
14 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Free fatty acids infl uence on aromatase gene expression in SVF cells Free fatty acids infl uence on aromatase gene expression in SVF cells Wojciech Dudek, Łukasz Wator, Adriana Balwierz, Urszula Razny and Aldona DembinskaKiec. Department of Clinical Biochemistry Jagiellonian University Medical College, Krakow, Poland Email: lw[email protected]w.pl Introduction: Adipose tissue is known as a secretive non only energy storing organ. Aromatase is one of the substances produced by adipose tissue. This enzyme is also expressed in in gonads, vessel wall cells. In adipose tissue the enzyme is expressed by stromal vascular fraction, not adipocytes. It is the main enzyme for estrogen syntase which drives androgens as androstenedione, testosterone and 16α-hydroxyandrostenedione to estrogen convertion. AIM of the study was to investigate infl uence of fatty acids on expression of aromatase gene in progenitor cells isolated from human adipose tissue – stromal vascular fraction cells SVF. Materials and Methods: SVF cells were isolated using modifi ed Hauner’s method. After adaptation (5-7 days) in Adaptation Medium (SVF-AM, DMEM + insulin + hydrocortisone + transferin) cells were stimulated to differentiate to adipocytes (SVF-Adipo, by 48h incubation with adipogenic factors: IBMX, insulin, dexamethasone and culturing in Adipo medium- (DMEM + insulin + hydrocortisone + transferin + triiodothyronine) or to endothelial cells (SVF-Angio, by 24h incubation in Angio mediumEBM+2%FCS). Then cells (SVF-AM, SVF-Adipo, SVF-Angio) were for 24 h incubated with non-toxic (10-30 μM) concentrations of fatty acids (FFA): arachidonic acid-AA, eicosapentaenoic acid-EPA, oleic acid-OA and palmitic acid-PA). After incubation with FFA, the relative aromatase gene expression was performed using real-time PCR. Results: OA upregulated aromatase gene expression while AA and EPA downregulatted it in AM medium (not differentiated SVF cells). In cells differentiated to adipocytes (Adipo medium) after incubation with fatty acids no differences in aromatase gene expression were observed, whereas in cells differentiated to angioblasts (Angio medium) PA and OA downregulated aromatase gene expression while AA and EPA upregulatted it. Conclusion: Fatty acids could differently regulate aromatase gene expression in SVF cells what depends on the type of fatty acid (polyand monounsaturated) and the stage as well as direction of cell differentiation. Acknowledgements: This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944) and Polish MNiI (N404 008 32/0237) project.
Lipgene – Diet, genomics, and the metabolic syndrome: 15 an integrated nutrition, agro-food, social and economic analysis Gene-nutrient interactions in the metabolic syndrome: SNPs in ADIPOQ, ADIPOR1 and ADIPOR2 interact with plasma SFA levels to modulate insulin resistance in metabolic syndrome patients Jane F Ferguson, Catherine Phillips, Audrey C Tierney, Jolene McMonagle, Pablo Pérez-Martínez, Catherine Defoort, Julie Lovegrove, Christian Drevon, Ellen Blaak, Aldona Dembinska-Kiec, Brita Karlström, Jose Lopez-Miranda and Helen M Roche. Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Dublin Email: jane.fer[email protected] Introduction/objectives Progression of the metabolic syndrome is determined by genetic and environmental effects. Genenutrient interactions may be important in modulating susceptibility to development of metabolic syndrome traits. Here, gene-nutrient interactions were examined in subjects with the metabolic syndrome to determine interactions between single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and its two receptors (ADIPOR1 and ADIPOR2), and plasma fatty acid composition on characteristics of the MetS. Materials and methods/aims The Lipgene human intervention study determined the effect of reducing dietary saturated fatty acid (SFA) intake, by replacement with monounsaturated fatty acids (MUFA) or as part of a low-fat (LF) diet for 12 weeks, to alter plasma fatty acid composition in 486 subjects with the MetS. Plasma fatty acid composition, insulin sensitivity as assessed by IVGTT, biomarkers of infl ammation, and ADIPOQ, ADIPOR1 and ADIPOR2 SNP genotypes were determined. Results In the whole cohort, four SNPs interacted with plasma SFA to signifi cantly associate with insulin and HOMA, while two SNPs interacted with plasma SFA to affect adiponectin levels. However, genderspecifi c analysis revealed that the association with insulin sensitivity was stronger in males than in females. The gene-nutrient interaction was strengthened by SNP combination into multi-locus genotypes, revealing sub-groups of individuals with modifi able insulin resistance phenotypes, whose insulin and HOMA changed signifi cantly over the intervention period depending on changes in plasma SFA. Conclusions Polymorphisms in ADIPOQ, ADIPOR1 and ADIPOR2 showed consistent interactions with plasma SFA which may modulate insulin sensitivity in the MetS. Gender may be an important factor in determining the strength of the effect. Funding acknowledgement This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944) (http://www.ucd.ie/lipgene)
16 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis EPA and DHA intakes in UK adults according to age, gender and income Rachael. A. Gibbs and D. Ian Givens. Nutritional Sciences Research Unit, School of Agriculture, Policy and Development, Faculty of Life Sciences, University of Reading, UK Email: r[email protected].uk, [email protected].uk Introduction In a study of UK adults, mean intake of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) was 244mg/d which was sub-optimal relative to targets1. Variation due to age, gender or socioeconomic differences remains unknown. Therefore the objective of this work was to examine trends in intakes of EPA+DHA in males and females according to age group in the main UK population and a low income subgroup. Materials and Methods Diet diary data from the National Diet and Nutrition Survey2 and Low Income Diet and Nutrition Survey3 were used to calculate intakes of fi sh (exc.canned tuna) and animal derived foods by age and gender. These data, coupled with values for fatty acid composition of each food type gave estimates of EPA+DHA intakes. Results EPA+DHA intakes for adults aged 19-24, 25-34, 35-49 and 50-64 years in the national population were 97, 172, 249 and 334mg/d respectively for males and 98, 136, 203 and 328mg/d respectively for females. Overall mean intake for males was 259mg/d and 226mg/d for females. In the LIDNS subgroup, overall mean EPA+DHA intake was 183mg/d for males and 199mg/d for females and according to age group, intakes for 19-34, 35-49, 50-64 and 65+ years were 134, 133, 247 and 209mg/d respectively for males and 127, 233, 212 and 204mg/d respectively for females. Conclusions A trend towards increasing intakes with age and modestly higher intakes in males than females is apparent in both groups. Intakes in the low income group are lower, although differing survey methods and age groupings do not allow full comparison. If eating habits do not change, today’s younger adults are likely to have vastly suboptimal intakes in the future. Acknowledgements This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944). Lipgene are gratefully acknowledged for funding this work. 1 Givens & Gibbs (2006) Nut. Bulletin 31 104-110 2 Gregory et al (2002) NDNS. 3 Nelson et al (2007) LIDNS.
Lipgene – Diet, genomics, and the metabolic syndrome: 17 an integrated nutrition, agro-food, social and economic analysis LDAP expression in skeletal muscle biopsies from subjects with the metabolic syndrome Ingrid MF Gjelstad, Fred Haugen, Kåre I Birkeland and Christian A Drevon. Department of Nutrition, University of Oslo, Norway. Email: i.m.f[email protected] Background Lipid droplet associated proteins (LDAPs) are found on the surface of intracellular lipid droplets in adipose tissue, skeletal muscles as well as other tissues. Five LDAPs have been described: Perlipin (PLIN), Adipofi lin (ADFP), TIP47 (M6PRBP1), S3-12 (KIAA1881) and OxPAT (LSDP5). Some of these proteins are necessary for triglyceride accumulation and hydrolysis in cells, and the gene expression can be regulated by fatty acids as well as other conditions. Increased amounts of intramuscular fat has been observed both in obese and trained, normal weight subjects. In obese subjects intramuscular lipid accumulation is associated with reduced insulin sensitivity. This work set out to determine whether there is any relationship between mRNA expression of LDAPs in skeletal muscle biopsies and: quantity and quality of dietary fat; body weight; physical activity level (PAL); and insulin sensitivity. Material and Methods mRNA expression of fi ve LDAPs was monitored in skeletal muscle biopsies (m. vastus lateralis) from 30 men and 32 women with the metabolic syndrome from Oslo, Maastricht, Uppsala and Dublin. The biopsies were taken before and after 3 months in the Lipgene human dietary intervention study (WP 1.2). Gene expression was analyzed by TaqMan Gene Expression Assays (RT-PCR, Applied Biosystems) using RPLP0 as endogenous control. Dietary intake was calculated from 3 days weighed food records before and after the intervention. PAL was calculated based on the Baecke questionnaire fi lled in at baseline. Preliminary Results At baseline there was a negative correlation between dietary intake of saturated fatty acids (%) and two LDAPs in men, but not in women (LSDP5: r=-0.58, p=0.001 and ADFP: r=-0.49, p=0.006). There was no correlation between total fat intake (%) and any of the LDAPs. A positive correlation existed between body weight (kg) and PLIN in men (r=0.57, p=0.001) as well as women (r=0.41, p=0.020). There was a negative correlation between PAL (arbitrary units, AU) and both LSDP5 (r=-0.72, p<0.001) and KIAA1881 (r=-47, p=0.017) in women, but not in men. There was also a negative correlation between fasting C-peptide and ADFP in men (r=-0.43, p=0.017), but it did not reach statistical signifi cance in women (r=-0.34, p=0.061). The correlation between fasting insulin and glucose with ADFP was not signifi cant, and there was no change in LDAP expression after 3 months of dietary intervention. Conclusions Preliminary baseline results show sex specifi c correlations between mRNA expressions of LDAPs in skeletal muscle biopsies, some dietary and biological parameters as well as physical activity level. mRNA levels of LDAPs did not change after 3 months of dietary intervention focusing on quality and quantity of dietary fatty acids. This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944), South-Eastern Norway Regional Health Authority and Johan Throne Holst Foundation for Nutrition Research.
18 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Journey to LC-PUFA in plants: moving from models to crops Richard P Haslam, Monica Venegas-Caleron, Olga Sayanova, Johnathan A Napier, Tony R Larson, Ian A Graham, Thorsten Zank and Joerg Bauer. CNAP, Department of Biology, University of York, UK. Email: [email protected] Humans are capable of only limited de novo synthesis of long chain polyunsaturated fatty acids (LCPUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Therefore the human diet must contain these essential fatty acids. In particular EPA and DHA derived from fi sh have been shown to improve human health. In particular it is suggested that n-3 LC-PUFA may reduce the risk of metabolic syndrome, a term used to describe a collection of pathologies indicative of a progression towards heart disease, diabetes, stroke and obesity, which constitutes an increasing public health problem in industrialised societies. The ability to produce such fatty acids in plants, as an alternative to marine sources, is therefore of considerable interest. Production of such fatty acids requires a biotechnological multidisciplinary approach in which a suite of genes, including novel desaturases, elongases and acyltransferases are introduced into plants in order to modify the oil. A process of gene discovery from a wide variety of organisms e.g. diatoms and fungi, has provided a portfolio of candidate genes with optimal substrate preferences and activities. Genes encoding these activities have been combined in cassettes and introduced into the model plant Arabidopsis. With LC-PUFA biosynthesis demonstrated at signifi cant levels in model plants, work then focused on the delivery of oils in an appropriate agricultural crop, Brassica napus or rapeseed. A combination of glass house and fi eld trials has confi rmed the utility of producing LC-PUFA in B. napus. We have demonstrated through this work how the modifi cation of plant oils can be achieved in crops of agricultural signifi cance. Acknowledgments This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944). Rothamsted Research receives grant-aided support from the Biological Sciences and Biotechnology Research Council (BBSRC) UK.
Lipgene – Diet, genomics, and the metabolic syndrome: 19 an integrated nutrition, agro-food, social and economic analysis Metabolic syndrome & psychosocial factors Stephanie Hodge and Barbara Stewart-Knox. Northern Ireland Centre for Food & Health University of Ulster, Coleraine, Northern Ireland. Email: [email protected].ac.uk Socio-economic and lifestyle factors are known to infl uence development of the metabolic syndrome and there is some evidence to suggest that stress and other negative psychosocial factors may also contribute. There is however very little evidence as to whether positive emotional factors, such as resilience or optimism, may or may not reduce the risk of developing metabolic syndrome. The aim of this study has been to explore potential associations between various positive and negative psychological, lifestyle and social factors in people with metabolic syndrome compared to healthy individuals. Data were collected by self-reported questionnaire from people aged 30 to 70 (n=200) previously screened for the Lipgene nutritional studies being carried out in Ireland (ROI), UK, and France (n=110) and also by direct approach a representative sample of the general public (n=90). Data were analysed using SPSS Version11.5 for Windows. Results are shown for psychosocial and lifestyle factors, and are discussed in relation to identifi cation of groups and areas for targeting of health promotion to prevent and treat metabolic syndrome. Funding acknowledgement This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944) and DEL, NI, as part of a PhD studentship.
20 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Effect of normal and high oleic rapeseed in the dairy cow diet on milk fatty acid composition Kirsty E. Kliem, David J. Humphries and D. Ian Givens. Animal Science Research Group, School of Agriculture, Policy and Development, University of Reading, Reading, UK. Email: [email protected] Introduction Milk and dairy products are the major source of saturated fatty acids (SFA) in the European diet and there is evidence that replacing SFA with cis-monounsaturated fatty acids (MUFA) will improve risk factors for cardiovascular disease. Rapeseed in dairy cow diets simultaneously reduces milk SFA and increases cis-MUFA, but also increases milk trans MUFA. A new variety of rapeseed with higher oleic acid content (therefore less potential for increasing milk trans-MUFA) was compared with a normal oleic acid rapeseed, and both compared with a control diet. Methods Seven early lactation multiparous Holstein-Freisian cows were randomly allocated to one of seven total mixed ration diets (50:50 forage:concentrate) for 5 x 28 day periods. The control diet contained 41 g/kg dry matter commercial lipid supplement and treatment diets contained one of two different rapeseeds (normal and high, oleic acid contents 58 and 70 g/100 g total fatty acids respectively) milled with wheat at three inclusion levels so that diets provided approximate intakes of 750, 1000 and 1250 g/ cow/day rapeseed oil. Milk fatty acid composition was analysed at the end of each period. Results Both rapeseeds decreased (P<0.001) milk SFA content from 66 g/100g fatty acids in control milk to 58 and 57 g/100g fatty acids for the highest dose of normal and high oleic rapeseed respectively. Corresponding increases in cis-MUFA (P<0.05) were seen (from 25 to 31 and 33 g/100g fatty acids). These responses were linear, and greater for the high oleic acid rapeseed. Milk trans-MUFA content was also increased by feeding both rapeseeds (P<0.05) but there was no difference between rapeseed types. Conclusions The results indicate that the high oleic acid rapeseed was superior to the normal at decreasing and increasing SFA and cis-MUFA respectively but this was still accompanied by increases in milk transMUFA. Acknowledgements This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944). The high oleic acid rapeseeds were donated by Dow AgroSciences Ltd.
Lipgene – Diet, genomics, and the metabolic syndrome: 21 an integrated nutrition, agro-food, social and economic analysis Estimation of current and projected omega-3 fatty acid intake with enriched food prototypes in The Netherlands, United Kingdom, and France Kati M Laitinen, Jennifer Eeuwijk, Susan HF Vermunt and Peter L Zock. Unilever Food & Health Research Institute, The Netherlands. Email: [email protected] Introduction A signifi cant part of the European population may not have intakes of omega-3 fatty acids at the level recommended for prevention of cardiovascular disease. This study provides an overview of the population average intakes of α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in The Netherlands, United Kingdom (UK) and France. Another objective was to investigate the potential impact of enriched food prototypes on the population average intake of these fatty acids. Materials and Methods The average intakes of ALA, EPA and DHA in the general healthy adult population were estimated by combining food intake data from national dietary surveys of each country with the fatty acid composition of foods as reported in respective national food composition tables. To estimate the potential impact of prototype foods (fat spreads and salad oils enriched with ALA; and poultry meat, fat spreads and salad oils enriched with EPA and DHA) on the intake of ALA and EPA and DHA it was assumed that prototypes would replace all equivalent regular foods. Results The estimated average intake of ALA was 1.6, 1.1 and 0.8g/d in the Netherlands, UK and France, respectively. The estimated average intake of EPA and DHA was 75, 246 and 226mg/d in the Netherlands, UK and France, respectively. With prototypes the potential intake of ALA was predicted to be 2.7, 1.8 and 0.9 g/d in The Netherlands, UK and France, respectively. Similarly the potential intake of EPA and DHA was predicted to be 461, 512 and 327 mg/d in The Netherlands, UK and France, respectively. Conclusion: The average intake of ALA, EPA and DHA is lower than recommended for the prevention of cardiovascular diseases. The availability of common, everyday foods enriched with ALA, EPA and DHA could help people achieve optimal omega-3 fatty acids intake levels. Funding: This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944) and Unilever
22 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Hyphenated-Chromatography techniques to monitor the oilseed metabolome during LC-PUFA synthesis Tony R. Larson, Valeria Gazda, Johnathan A. Napier, Thorsten Zank and Ian A. Graham. CNAP, Department of Biology, University of York, UK. Email: [email protected].uk Introduction Crop species such as oilseed rape do not accumulate long-chain polyunsaturated fatty acids (LC-PUFAs) in their seed triacylglycerols (TAGs). LC-PUFAs such as eicosapentaenoic acid (EPA) can be produced if novel desaturases and elongases are identifi ed and expressed in developing seeds1. The success of this approach requires the iterative integration and co-ordinate expression of these genes to reconstitute the LC-PUFA pathway. To inform the success of this and other approaches we have developed a platform of technologies to discover the bottlenecks in LC-PUFA production in metabolically engineered oilseeds. Materials and Methods A Brassica napus line expressing several desaturases and elongases from heterologous sources was used to evaluate LC-PUFA pathway activity in developing seeds. In addition, an Arabidopsis thaliana LC-PUFA line producing low levels of EPA was subjected to large-scale mutagenesis to introduce genetic variation and subsequently screened for enhanced EPA production. Seed material was profi led using hyphenated chromatography platforms developed for TAG, acyl CoA, and fatty acid methyl ester (FAME) analyses. Results Analyses of B.napus seed showed that LC-PUFAs generally accumulated on only one of the three available TAG positions. This suggests that acyltransferase engineering in addition to desaturase/ elongase expression is required to maximize LC-PUFA production. The accumulation of acyl-CoA intermediates, specifi cally delta-6 elongase substrates, also suggested that this elongation step was sub-optimal. Finally, FAME screening of the mutagenized A thaliana population showed that further increases in LC-PUFA yield are possible. Conclusions: Metabolite profi ling platforms have proved invaluable to guide the process of LC-PUFA metabolic engineering in oilseeds. Candidate lines can be evaluated not only in terms of LC-PUFA yield, but also to discover what specifi c biochemical steps require further optimization. Acknowledgements This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944). This work was performed as part of Lipgene, an EU Sixth Framework Integrated Programme. 1 Graham et al, 2007. Curr. Opin. Biotechnol. 18:142-147
Lipgene – Diet, genomics, and the metabolic syndrome: 23 an integrated nutrition, agro-food, social and economic analysis Dietary habits and metabolic syndrome in middle-aged europeans Heather Parr, Barbara Stewart-Knox, Bunting B, Gilpin S, Pinhão S and de Almeida MDV. Northern Ireland Centre for Food and Health, University of Ulser, Coleraine. Email: [email protected].ac.uk Metabolic syndrome may be dietary related1. The aim of this analysis has been to explore associations between dietary habits, body fat distribution and patterns in the reporting of conditions related to metabolic syndrome in European consumers. Data were collected by survey from a representative sample aged ≥40 years (n 1722) in GB (n 1182) and Portugal (n 540) as part of the Lipgene project. Waist circumference (WC) and BMI were measured. A short Food Frequency Questionnaire (FFQ) was employed to assess dietary habits for major food groups. FFQ data were factor analysed, and selfreported conditions associated with metabolic syndrome (high blood cholesterol, high blood pressure, mid-waist obesity, high/low blood sugar) and anthropometric measures underwent Latent Class Analysis Mplus©2. Based on FFQ factor analysis three clusters of dietary habits emerged: ‘alcohol rich’ with infrequent intake of fruit and vegetables or other food groups; ‘unhealthy’ frequent consumption of high-fatcontaining foods and infrequent alcohol; and, ‘healthy’ with wine consumption (infrequent intake of other alcohol) and consumption of a variety of food groups including fi sh and low-fat-containing foods. Four latent classes emerged from patterns of self-reported metabolic syndrome signs (‘metabolic syndrome’ (22%), BMI29.9, WC97.9cm, ‘healthy’ (no symptoms) (58.4%) BMI24.9 WC84.8cm; ‘overweight’ (15%), BMI28.4, WC92.5cm; ‘obese’ (4.6%), BMI35.9, WC102.2cm). One way ANOVAs were conducted to determine differences between four metabolic syndrome latent classes in relation to three dietary profi les. The ‘metabolic syndrome’ class were less likely than the ‘overweight’ class to be in either the ‘unhealthy’ (p=0.000) or ‘alcohol rich’ (p=0.023) dietary group and the ‘metabolic syndrome’ class were less likely than the ‘healthy’ class to be in the ‘unhealthy’ (p=0.000) or ‘alcohol rich’ (p=0.007) dietary groups. The fi ndings could suggest that those reporting signs of metabolic syndrome are not defi ned by unhealthy dietary habits. Frequent alcohol consumption appears to be a marker for infrequent food consumption and infrequent alcohol a marker for intake of high-fat foods, while wine intake may be a marker for a healthy balanced diet. This theory requires further investigation. This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944). 1 Buttriss J & Nugent A (2005). Lipgene: an integrated approach to tackling the metabolic syndrome. Proceedings of the Nutrition Society 64(3): 345-347. 2 Muthén BO & Muthén LK (2006) MPlus statistical Analysis with Latent Variables: User’s guide. 4th Edition. LA, CA. 3 Survey Fieldwork was sub-contracted to Ipsos MORI (GB). This work was completed on behalf of the Lipgene Consortium and funded under the EU 6th Framework Food Quality and Safety Programme, code FOODCT-2003-505944.
30 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Effects of dietary fat modifi cations on insulin sensitivity and metabolic markers of the metabolic syndrome. Lipgene – a randomised European dietary intervention study Audrey C Tierney, Jolene McMonagle, Danielle I Shaw, Hanne L Gulseth, Catherine Defoort,Wim H.M Saris, Juan A Paniagua, Iwona Gołãbek-Leszczyn´ska, Denis Larion, Christine M Williams, Brita Karsltröm, Bengt Vessby, Aldona Dembinska-Kiec, José López Miranda, Ellen Blaak, Christian A Drevon, Michael J Gibney, Julie A Lovegrove and Helen M Roche. Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Republic of Ireland. Email: [email protected] Objective Dietary saturated fatty acids (SFA) may promote insulin resistance. Lipgene investigated the metabolic effects of substituting dietary SFA by replacement with monounsaturated fatty acids (MUFA) or as part of a low-fat (LF) diet in subjects with the metabolic syndrome. Materials and Methods 417 free-living subjects with the metabolic syndrome were randomly assigned to one of four isoenergetic diets distinct in fat quantity and quality; high-SFA (HSFA); high-MUFA (HMUFA) and two low-fat, high complex carbohydrate (LFHCC) diets, supplemented with 1.24g/day of long chain omgea-3 PUFA (LC n-3 PUFA) or placebo for 12 weeks. Results Pre-treatment habitual dietary fat composition had a marked effect on markers of insulin sensitivity. The HSFA diet adversely affected insulin sensitivity, particularly in females (P=0.022), and increased Sicam concentrations (P=0.05) in subjects who habitually consumed a low-fat diet (<36% energy from fat). In contrast the HMUFA diet improved HOMA-IR and the insulin:c-peptide ratio in subjects who habitually ate a high-fat diet (P=0.024 and P=0.001, respectively). Furthermore omega-3 PUFA supplementation with a LFHCC omega-3 PUFA diet reduced plasma triacylglycerol (TAG) and nonesterifi ed fatty acid (NEFA) concentrations (P<0.01), and the atherogenic index (P=0.03), an effect most evident in men. Conclusions The Lipgene intervention study showed that fat composition can modulate markers of the MetS which is dependent on habitual fat intake such that SFA had detrimental and MUFA benefi cial effects on insulin sensitivity, particularly in women. The LFHCC omega-3 PUFA diet improved lipid related metabolic syndrome risk profi les particularly in men. Thus nutrition strategies can improve the metabolic phenotype of subjects with the metabolic syndrome within the context of an overweight/ obese phenotype. This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944).
Lipgene – Diet, genomics, and the metabolic syndrome: 31 an integrated nutrition, agro-food, social and economic analysis Effect of dietary fat modifi cation on skeletal muscle fatty acid handling in the metabolic syndrome; a stable isotope approach Anneke MJ van Hees, Wim HM Saris, Gabby B Hul, Nicolaas C Schaper, Bas E Timmerman, Helen M Roche and Ellen E Blaak. Department of Human Biology (NUTRIM), Maastricht University, The Netherlands. Email: anneke.v[email protected] Introduction In the metabolic syndrome, adipose tissue lipid buffering capacity may be disturbed, resulting in increased lipid overfl ow in the circulation and increased fat storage in ‘non-adipose’ tissue like skeletal muscle, which may be related to insulin resistance. Therefore, the aim of this study was to examine the effects of chronic dietary fat modifi cation on the capacity of skeletal muscle to handle dietary and endogenous fatty acids (FA) in the metabolic syndrome. Methods In a sub-cohort of the Lipgene study, 39 men (58±2yr, BMI 30.3±0.7kg/m) with the metabolic syndrome were randomly assigned to receive one of four diets for 12 weeks: a high-fat saturated fat diet (HSFA), a high-fat mono-unsaturated fat diet (HMUFA), and 2 low-fat high-complex carbohydrate diets, either supplemented with placebo (LF) or 1.24g/d DHA/EPA (LFn-3). Effects of the diets on fasting and postprandial skeletal muscle FA handling were examined by measuring arterio-venous differences across skeletal muscle. Briefl y, [H2]-palmitate was infused intravenously to label endogenous fat in the circulation and subjects received a high-fat mixed meal (providing 2.6 MJ, 61 E% fat, 35.5 E% SFA) containing [U-C]-palmitate to label chylomicron-TAG. Insulin sensitivity was measured with an insulinmodifi ed intravenous glucose tolerance test. Results No differences were observed in insulin sensitivity nor in postprandial insulin and glucose concentrations between the diets. However, postprandial circulating TAG concentrations were signifi cantly lower in the LFomega-3 group than the HSFA group and we observed lower concentrations of [U-C]-labelled TAG, representing total chylomicron-TAG. No differences were observed in skeletal muscle FA handling between the diets. Conclusions The LFomega-3 diet resulted in decreased postprandial TAG concentrations, which seemed to be due to a lower accumulation of dietary FA in the circulation. This is not accompanied by a higher clearance in skeletal muscle, suggesting that a higher uptake of chylomicron-TAG by adipose tissue or a lower intestinal TAG absorption may be responsible for this. Funding acknowledgements This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944) (www.ucd.ie/ ipgene).
32 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Correlation of rumen microbial community structure with milk fatty acid composition Graham Horgan and R. John Wallace. University of Aberdeen Rowett Institute of Nutrition and Health, Bucksburn, Aberdeen, UK Email: [email protected], [email protected] Introduction: Biohydrogenation of fatty acids in the rumen converts health-promoting polyunsaturated fatty acids consumed by the grazing cow to less healthy saturated fatty acids, which eventually make up the majority of fatty acids in ruminant products, including meat and dairy products. The aim of this work was to try to understand how the microbial population of the rumen infl uences milk fatty acid composition. Materials and Methods: Milk composition data from seven dairy trials carried out at the University of Reading and at MTT, Jokioinen, Finland, were compared with qPCR analysis of the main known biohydrogenating bacteria of the rumen using principal component analysis. Results: Across-trial analysis indicated some correlations between concentrations of individual fatty acids in milk and the numbers of different bacterial species, but these were generally for minor components of milk, and no correlation was evident between the bacterial community and the main groups of fatty acids in milk, either individually or collectively. The basal diet was the main determinant of milk fatty acid composition across trials. Within individual trials, where the basal diet was similar, there was a stronger link between microbial community composition and fatty acid content of milk. Conclusions: Strategies aimed at controlling milk fatty acid composition by manipulation of the microbial community in the rumen are likely to be less effective than altering the composition of the basal diet. This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944).
Lipgene – Diet, genomics, and the metabolic syndrome: 33 an integrated nutrition, agro-food, social and economic analysis Dietary supplementation of tetradecylthioacetic acid increases feed intake, but reduces body weight gain and adipose depot sizes in rats fed high-fat diets Andreas J. Wensaasa, Arild C. Rustanb, Merethe H. Rokling-Andersena, Jørgen Jensenc, Olav Kaalhusd, Bjørn A. Graffe, Oddrun A. Gudbrandsenf, Rolf K. Bergef,g and Christian A. Drevona. Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway. Email: [email protected] Aim: The pan-PPAR ligand and fatty acid analogue tetradecylthioacetic acid (TTA) may reduce plasma lipids and enhance hepatic lipid metabolism, as well as reduce adipose tissue sizes in rats fed highfat diets. This study further explores the effects of TTA on weight gain, feed intake and adipose tissue functions in rats fed a high-fat diet up to 7 weeks. Methods: The effects on feed intake and body weight during 7 weeks dietary supplement with TTA (~200 mg/kg bw) was studied in male Wistar rats fed a lard-based diet containing ~40% energy from fat. Adipose tissue mass, body composition and expression of relevant genes in fat depots and liver were measured at the end of the feeding. Results: Despite enhanced feed intake, rats fed TTA gained less body weight than lard-fed rats and had markedly decreased subcutaneous, epididymal, perirenal and mesenteric adipose depots. The effects of TTA-feeding with reduced body weight gain and energy effi ciency (weight gain/feed intake) started between day 10 and 13. Body content of fat, protein and water was reduced after feeding TTA, with a stronger decrease in fat relative to protein. Plasma lipids, including NEFA, were signifi cantly reduced, whereas fatty acid ß-oxidation in liver and heart was enhanced in TTA-fed rats. Ucp3 was expressed ectopically (>1900-fold) in livers, whereas Ucp1 was increased ~30-fold in epididymal and ~90-fold in mesenteric fat after TTA-feeding. Conclusion: Our data support the hypothesis that TTA-feeding may increase hepatic fatty acid ß-oxidation, thereby diminishing storage of fat in adipose tissues. The increased expression of hepatic Ucp3 and of Ucp1 in abdominal adipose tissues may together promote enhanced energy dissipation and reduced weight gain in rats. Funding This work was supported by Lipgene, an EU Sixth Framework Programme Integrated Project (Project number: FOOD-CT-2003-505944).
34 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis
Lipgene – Diet, genomics, and the metabolic syndrome: 35 an integrated nutrition, agro-food, social and economic analysis Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis
36 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Background to the Project 1.0 Introduction Each year the number of obese Europeans is increasing, and this is having a serious impact on health. Obesity causes a number of metabolic disturbances that can adversely affect an individual’s chance of suffering from other chronic diseases later in life. People who are overweight or obese are more likely to suffer from coronary heart disease, type 2 diabetes and high blood pressure. This clustering of risk factors is referred to as the metabolic syndrome. Within the UK alone, it is thought that as many as 25% of the population show clear signs of this syndrome, and there is little doubt that this is also the case in many European countries. Unless effective public health strategies are enforced, it is expected that the prevalence of the metabolic syndrome will continue to increase, bringing with it a dramatic rise in health and social welfare costs needed to treat the condition. A note about obesity Overweight and obesity are defi ned as ‘abnormal or excessive fat accumulation that presents a risk to health’ . The Body Mass Index (BMI) is one of the most common tools used to defi ne obesity. BMI = weight (kg) height (m)2 A person with a BMI of over 25kg/m2 is said to be overweight, and those with a BMI greater than 30kg/m2 obese. Whilst the prevalence of obesity within Europe has been on an upward trend for some time, there is evidence to suggest that this increase has become more marked in recent years3. Within the 15 countries that made up the EU in 2002, an estimated 18% of men and 21% of women were obese. This varied within countries, with Austria topping the list with an alarming 30% of men and 26% of women being obese. Conversely, the rates in the Scandinavian countries were relatively low (approximately 15% of men and 16% women). Projecting current obesity trends to 2025, it is estimated that a staggering 30% of men and 34% of women will be obese unless something is done to halt this rise4. Within the UK, the government predicts that if current trends continue, by the year 2050 over half of the population will be obese5; there is little doubt that similar trends will not be seen across all EU Member States. Not only does obesity seriously impact upon the mental wellbeing and quality of life of those affected6, it also predisposes them to a number of chronic diseases, which together constitute the principle causes of death in the developed world7. These include: cardiovascular disease (CVD) (which includes coronary heart disease (CHD) and stroke); cancer8; and type 2 diabetes9. Obesity cost the European economy an estimated €32.8 billion in 2002. This fi gure includes the costs associated with treating the complications of obesity and lost productivity from days taken off sick. Unless something is done to stop the predicted increase in the prevalence of obesity in Europe, the consequences for both health and the economy are likely to be severe. Obesity and its related complications may end up costing the EU up to 6% of its health care budget by the year 20254.
Lipgene – Diet, genomics, and the metabolic syndrome: 37 an integrated nutrition, agro-food, social and economic analysis 2.0 The Metabolic Syndrome The metabolic syndrome (or syndrome X) is a term used to describe a cluster of metabolic disorders which increases an individual’s risk of suffering from CVD and type 2 diabetes10. These disorders commonly include insulin resistance, hyperglycaemia, central obesity and hypertension. Currently, no accepted defi nition of the metabolic syndrome exists, although a number of different diagnostic criteria have been proposed by different organisations11, 12, 13. Despite this lack of a standard defi nition, central to all diagnostic criteria is the fact that sufferers experience some degree of impaired glucose tolerance and insulin resistance. Further symptoms of the syndrome may also include: Central/abdominal obesity Raised blood pressure/hypertension Dyslipidaemia (abnormal blood lipids) Gout Abnormalities in blood clotting Low cardio-respiratory fi tness Presence of fatty liver disease or polycystic ovary syndrome A note about insulin – Insulin is a hormone produced by the pancreas in response to food intake. Insulin circulates in the blood and regulates the movement of glucose into cells. Once inside the cell, glucose is used as an energy source, or stored as glycogen until needed. Insulin resistance is a condition whereby the body’s cells are less sensitive to the action of insulin. It occurs when insulin is secreted as normal by the pancreas, but it does not carry out its usual function as outlined above. As a result, the amount of glucose in the blood becomes too high (hyperglycaemia). To try and overcome this problem and maintain normal blood glucose levels, the pancreas secretes additional insulin but, for some people, the body’s cells still do not respond. This situation leads to insulin resistance, and type 2 diabetes often consequently develops from prolonged elevated blood glucose levels.
38 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis The underlying cause of the metabolic syndrome is unknown, but insulin resistance and obesity are thought to be key. Possible theories have included the idea that insulin resistance may be the primary event leading to its onset. However, other theories suggest that it is the onset of obesity that is responsible for disturbances in carbohydrate and lipid utilisation in tissues, and insulin resistance is second to this10. Whatever the initial cause, the rising obesity levels seen in EU countries consequently result in a population at an increased risk of developing type 2 diabetes – indeed, approximately 80% of people diagnosed with type 2 diabetes are overweight14. Due to a lack of a universally accepted defi nition for the metabolic syndrome, estimating its prevalence is often diffi cult. However, in the US, data from the National Health and Nutrition Examination Survey show that the prevalence of the metabolic syndrome increased from 23.1% in the period 1988-1994, to 26.7% in 1999-200015. It is thought these fi gures may be an underestimation of the actual prevalence as, due to the complex process involved in the development of the disease, many cases are believed to go undiagnosed16. Within the UK, it is thought that as many as 25% of the adult population show clear signs of the syndrome1 and, due to the fact that the burden of obesity may be the driving force behind the metabolic syndrome, it is likely that the prevalence within the population will increase in parallel with the rising incidence of obesity. Within a population, there is a marked difference in prevalence between different subgroups. The risk of developing the metabolic syndrome increases with age, with the metabolic syndrome chiefl y being thought of as a disease of middle and old age17. In more recent years however, cases of children showing signs of type 2 diabetes have been emerging18. Another subgroup of the population at an increased risk of the syndrome is certain ethnic subgroups. This is exemplifi ed in a study which found the prevalence of the syndrome to be higher in South Asians when compared to Europeans19.
Lipgene – Diet, genomics, and the metabolic syndrome: 39 an integrated nutrition, agro-food, social and economic analysis 3.0 Dietary Fat Dietary fat is essential for overall health and wellbeing. Why we need fat It acts as an energy source for the body It enhances the fl avour and palatability of food It is the source of essential fatty acids It acts as a carrier for fat soluble vitamins However, dietary fat, the most energy dense nutrient (providing 9kcal/g) can make a substantial contribution to energy intakes and may infl uence the development of various chronic diseases, including obesity and the metabolic syndrome. It is for this reason that getting the correct amount and type of fat in the diet is critical if we are to reduce the burden of these chronic diseases. The fatty acid chains which make up dietary fat comprise a chain of carbon atoms, with a methyl group at one end and a chain of carbon atoms at the other. The nature of the fatty acids, and therefore the fat, depend upon whether these carbon atoms are saturated with hydrogen, or not (unsaturated). All fats and oils regardless of their source comprise a mixture of different types of fatty acids, but the ratio of the different types varies. Unsaturates can be further subdivided into two types: monounsaturates (MUFA) and polyunsaturates (PUFA). MUFAs are characterised due to the presence of one double bond in their carbon backbone, whereas PUFAs may have two or more double bonds. PUFAs can be further categorised, with the two main groups being the omega-3 (or n-3) and omega-6 (or n-6) fatty acids. Two particular fatty acids, alpha-linolenic acid (omega-3) and linoleic acid (omega-6) are termed ‘essential’ fatty acids, as they cannot be synthesised by the body, and therefore must be provided by the diet.
46 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Aim: to gain an understanding of the factors involved in the development of the metabolic syndrome, and to provide an approach to its effective management and prevention. More specifi cally: To understand the manner in which differences in the composition of dietary fat interacts with natural human genetic variation to infl uence the development of the metabolic syndrome To create alternative plant sources of long chain omega-3 polyunsaturates, by taking genes from marine algae to produce a seed-oil containing the vital long-chain omega-3 PUFA usually found in fi sh oil To establish the principles of animal nutrition, which change the composition of milk fat from dairy cows to one with less saturates, less trans fats and more monounsaturates. In addition, animal nutrition research will increase the supply of long-chain omega-3 PUFA enriched poultry meats to provide additional sources of these fats To examine the economic barriers to introducing new agro-food technologies and the economic costs of the management of the metabolic syndrome through diet versus pharmaceutics To ascertain the concerns and views of the consumer as to the risks arising from the metabolic syndrome and the attitudes regarding the risk benefi ts of introducing new agro-food technologies to combat the metabolic syndrome To increase consumer awareness about the metabolic syndrome and associated health risks To complete a wide-ranging and high-level dissemination programme to: create awareness of the need to integrate diet and genetics in addressing the metabolic syndrome; and create awareness of the potential of new agro-food technologies to help combat the metabolic syndrome To provide a greater availability of food products that can enhance human health In the following sections, each of these different areas of research is focused upon in more detail.
Lipgene – Diet, genomics, and the metabolic syndrome: 47 an integrated nutrition, agro-food, social and economic analysis 7.1 Human Nutrition Studies The human nutrition intervention arm of Lipgene is composed of three main strands, all of which are discussed below. A Prospective Cohort The fi rst part of the human nutrition studies involves the use of a pre-existing cohort of subjects to track the development of the metabolic syndrome. As the clinical end-points of this study are relevant to the interaction between genes and the metabolic syndrome, the cohort has been used in Lipgene to retrospectively study the development of the metabolic syndrome and diet-gene interactions. The SUVIMAX study Short for: SUppléments en VItamines et Minéraux AntioXydants (Antioxidant Vitamin and Mineral Supplements) Began in 1994 13,000 participants, men and women aged 35-60 years living all over France Aim: to evaluate the effect of antioxidants on coronary heart disease and cancer incidence. In 2001-2002 Lipgene identifi ed 877 cases of the metabolic syndrome within this cohort, and 877 matched controls were also found. Genetic characteristics, baseline dietary analysis and baseline plasma fatty acid levels were amongst some of the markers compared between the groups, in a bid to identify potential dietary and genetic variables associated with the metabolic syndrome. Generally, cases had lower levels of educational attainment that controls, and were more likely to be smokers and less physically active. They also had a higher mean BMI at baseline, and had higher levels of fasting glucose and insulin (risk factors for the metabolic syndrome) and lower fasting HDL-cholesterol. Comparison of dietary intake showed that cases had a lower total daily energy intake at baseline than controls, to which the contribution of alcohol and protein to total daily energy intake were higher and carbohydrate lower in cases than controls. The contribution to energy intake of lipids and saturates between the two groups was similar, although cases were found to have slightly higher intakes omega-6 PUFAs than controls. The cases and controls were also genotyped, and genetic analysis undertaken to try and identify any genes, and pertinent single nucleotide polymorphisms (SNPs) within each gene, which may be associated with the development of the metabolic syndrome. Based on a list of 182 candidate genes and 806 SNPs initially being identifi ed, 7 SNPs in 6 genes were found to be signifi cantly different between subjects with the metabolic syndrome and matched controls. 3 of them, related to lipid metabolism or infl ammation, seem particularly implicated. Due to the complexity of this disease, more powerful data analyses are on-going to better defi ne effects of dietary or genetic factors.”
48 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis A Dietary Intervention The Lipgene human dietary intervention study was conducted to determine the effect of reducing intake of saturated fat (either in terms of reducing quantity or exchanging for MUFA) on multiple metabolic and molecular risk factors of the metabolic syndrome. Key metabolic markers determined included insulin sensitivity, lipid metabolism in the postprandial state, markers of infl ammation, coagulation and vascular function, and cellular energy status. The second aim was to identify if common genetic polymorphisms involved in the metabolic syndrome determined whether an individual responded to dietary therapy. Overall, 417 volunteers from eight cities across Europe, completed a 12-week intervention were they were randomised to one of four diets: A: high-fat, saturaterich (HSFA); B: high-fat, monounsaturaterich (HMUFA); C: low-fat, high-complex carbohydrate (LFHCC); and D: LFHCC with with long-chain n-3 PUFA. Dietary analysis showed that subjects adhered well to the interventions. Following the 12-week dietary intervention period, it was shown that subjects following both LFHCC diets lost a small amount of weight (<1 kg), despite the isoenergetic intervention. In the full cohort lowering SFA did not affect insulin sensitivity. However, when the effect of background diet on responsiveness to dietary intervention was examined there was a clear adverse effect of SFA on insulin sensitivity in individuals who habitually consume less than 36% of energy from fat. Also the LFHCC n-3 PUFA diet signifi cantly improved several indices on lipid metabolism. On-going genetic bioinformatic analysis highlights important infl ammatory genes which interact with dietary fat to determine insulin sensitivity – which indicates that genes can alter the effect of dietary fat modifi cation. Mechanistic Studies The fi nal part of the human nutrition studies aimed to investigate the role that dietary fatty acids play in the basic biology of the metabolic syndrome using animal and cell models. State of the art biology technology has been used to investigate the role of numerous different cellular processes in the development of the metabolic syndrome. These include: 1) the infl uence of fatty acid composition on adipogenesis – a key process involved in the development of insulin resistance and metabolic syndrome. 2) the role of fatty acids on human skeletal muscle cell fatty acid uptake– skeletal muscle is the primary organ involved in glucose disposal. 3) Atherogenesis and hypertension are both associated with insulin resistance, and endothelial function is a key regulator of these processes. Publications arising from these studies have been listed at the end of the report. A number of students and post doctoral researchers presented posters on these studies at the conference in Dublin (5th Dec 08). The abstracts are listed at the beginning of this booklet.
Lipgene – Diet, genomics, and the metabolic syndrome: 49 an integrated nutrition, agro-food, social and economic analysis 7.2 Plant Biotechnology The ultimate goal of the plant biotechnology group of Lipgene is to establish a sustainable source of long-chain omega-3 PUFAs for human consumption. Whilst oily fi sh provides a valuable source of these compounds in the diet, consumption of fi sh is low in many parts of the EU39, and there are concerns over long-term sustainability. Therefore, scientists in this arm of Lipgene aimed to investigate the potential of genetic engineering (see appendix 1 for more information) to create transgenic plants which contain a substantial proportion of long-chain omega-3 PUFAs. Producing long-chain omega-3 PUFAs in seed oil has many advantages over fi sh oil, including: a lower odour; less environmental contamination; and the fact that plants are a sustainable and cheap source of fatty acids. Using genes that regulate the production of EPA and DHA in marine algae, it was demonstrated that the omega-6 PUFA arachidonic acid (AA) and EPA could be produced in linseed. However, at only 5%, the concentration of these long-chain PUFA in the seed oil was too low for commercial use. Further, the ratio of omega-6 and omega-3 in these seeds needed to be optimised (a 5:1 ratio of omega-6:omega-3 is thought most benefi cial for human health). Scientists working in this area have identifi ed genes within rapeseed that are responsible for this ‘bottle-neck’ in the synthesis of long-chain PUFAs, and new genes associated with the biosynthesis of long-chain omega-3 PUFAs have also been identifi ed. This has enabled the production of a strain of rapeseed oil with a fatty acid composition optimised towards omega-3 fatty acids, and also allowed an increased yield of omega-3. As well as producing these modifi ed oils for human consumption, the possibility of using these oils in animal feed as part of the animal nutrition work was also discussed, with a view to enhancing the fatty acid profi le of meat products by using a sustainable source of omega-3 rich oils (see below).
50 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis 7.3 Animal Nutrition There is a general consensus amongst scientists and health care professionals that diets high in saturates increase an individuals risk of suffering from the metabolic syndrome24. Animal derived fats, including milk and dairy products, and meat and meat products, are often found to be the greatest contributor of saturates in the diet40. However, whilst these animal derived foods are a major contributor to the population’s intake of saturates, they also make a signifi cant contribution to intakes of monosaturates and other key nutrients. In addition there is good epidemiological evidence that milk has some cardioprotective effects. Therefore, reducing their intake is not always desirable. The initial aim of the animal nutrition strand of Lipgene is to improve the dietary fatty acid profi le of European consumers by modifying the fat content of two different foods: milk and poultry meat. For milk, the aim is to increase the content of monounsaturates, whilst simultaneously reducing the content of saturates, and at the same time avoiding or minimising an increase in trans fatty acids. Poultry meat was chosen as another potential vehicle to improve the fatty acid profi le of EU consumers for a number of reasons: the meat has gained consumer and health care professional approval in recent years due to the fact it is lean, yet contains signifi cant amounts of monoand polyunsaturates. This is refl ected by the fact that, whilst the consumption of ruminant meat has fallen signifi cantly over the last decade, consumption of poultry meat has substantially increased. The changes in meat consumption in the UK over the past 40 years 0 50 100 150 200 250 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 Individual weekly intake (g) Beef and Veal Mutton and Lamb Pork Bacon and Ham Poultry Sausages Source: DEFRA 2007 41
Lipgene – Diet, genomics, and the metabolic syndrome: 51 an integrated nutrition, agro-food, social and economic analysis Past attempts to enrich poultry with EPA and DHA have often relied upon fi sh oils. However, with this comes a concern about reduced shelf-life of the meat, problems with sensory properties of the poultry, and a worry over the long-term sustainability of fi sh oils for use for this purpose. To overcome these problems, Lipgene scientists are currently trying to enrich poultry meat using unique sources of EPA and DHA, which will need to have a satisfactory oxidative stability and an acceptable taste. The animal nutrition work has progressed well over the fi ve years. Alteration of the fatty acid content of milk has now been achieved. However the reduction in saturates and increase in monounsaturates has also come with a small but possibly undesirable increase in the trans fatty acid content. This problem will continue to be investigated further. With regards enrichment of poultry meat, whilst the initial plan was to use enriched rapeseed oil produced in the plant biotechnology workpackage as feed for the chickens, the amount of oil produced from this workpackage was small, therefore an alternative source of EPA and DHA was sought. Marine algae, the source of long-chain omega-3 polyunsaturates in the aquatic food chain, was the chosen alternative. Enrichment of poultry meat using this source of EPA and DHA has been achieved, and results show that this meat has the potential to meet recommendations for population omega-3 and omega-6 intakes if consumed at current levels. There is also the potential to further enrich this poultry meat beyond the target initially set, and this continues to be investigated.
52 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis 7.4 Economics As part of this workpackage, consortium members aimed to assess the direct and indirect costs of the metabolic syndrome, and to identify potential savings that could be made as a result of interventions identifi ed by Lipgene. Direct costs include staff time treating patients with the metabolic syndrome and the cost of drugs for treatment, and indirect costs associated with the metabolic syndrome include time off work due to illness, and premature death. There are signifi cant health care costs associated with obesity, with estimations suggesting that, in 2002, the cost of obesity and its associated conditions in the EU (then 15 member states) was around €32.8 billion4. By modifying the type and quantities of fats found in foods, it is hoped that EU consumers can modify their fatty acid intake, and thereby reduce the risk of getting diseases such as the metabolic syndrome. However, these modifi ed (often called ‘functional’ foods) are expensive to produce and the products are therefore sold at a premium. Reasons for this high cost include: the higher cost of the ingredients needed to produce the food (i.e. feeding fi sh oil to cows); the additional cost imposed on farmers; and the need for dedicated supply chains for these products so they do not become contaminated with other products. Estimations suggest that these functional foods could cost between 35-85% more than their standard counterparts. As consumers may not be willing, or maybe unable, to pay these increased prices, subsidising these foods may be necessary. The cost of this would therefore need to be offset against the potential healthcare savings that would be made as a result of consuming these products. Estimates from this strand of Lipgene indicate that subsidising the cost of purchase of these healthier foods would be economically favourable when compared to the cost incurred by the metabolic syndrome.4
Lipgene – Diet, genomics, and the metabolic syndrome: 53 an integrated nutrition, agro-food, social and economic analysis 7.5 Consumer Understanding and Awareness The consumer science work of Lipgene has two main points of focus: 1) to construct a psychometric model of the metabolic syndrome, demographic, lifestyle and psychological factors;2) to conduct a quantitative survey of consumer attitudes to interventions to prevent and treat the metabolic syndrome. Focus groups and interviews involving EU consumers and stakeholders were also held to explore these aims. Evidence is accumulating to suggest that the metabolic syndrome may be triggered and/ or exacerbated by psycho-social factors. How these factors interacted in the aetiology of the metabolic syndrome was relatively unclear, therefore Lipgene aimed to identify a model to determine causal links between the metabolic syndrome and these psychological risk factors. A representative survey of late middle-aged people was conducted in Portugal (N+500) and Great Britain (N=1000). The survey included a range of validated psychometric scales to measure resilience, stress, depression and mood. Enquiry was made of physical activity, dietary habits and life events. Anthropometric measures were also taken. Findings indicate that people who are older, inactive, have experienced negative life events, and who are less resilient, are more likely to have the metabolic syndrome. Consumer perceptions of the metabolic syndrome and associated health issues, as well as attitudes towards potential interventions including functional foods, GM technology and personalised nutrition, were evaluated in a 6-country survey42. of nearly 6000 participants in France, Great Britain, Germany, Italy, Poland and Portugal. There was a good awareness of dietrelated diseases, although only 31% knew of the term metabolic syndrome. When asked to select from a list of ‘functional foods’, those found to be commonly consumed included fruits and vegetables, with a quarter of the sample claiming to drink probiotic yoghurt drinks. Whilst past research from this area have shown consumers often have a negative attitudes towards GM foods, this survey found that one-third of participants would accept GM foods if they provided health benefi ts. Tests investigating the acceptance of genetic testing found that two-thirds of participants were willing to have a genetic test to identify their risk of type 2 diabetes/heart disease43, 44.
54 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis 7.6 Dissemination An essential part of the Lipgene work is disseminating the fi ndings of the project to the general public. The British Nutrition Foundation is responsible for this part of the Lipgene project, and information from the project has been presented in many different ways. These include the production of a bi-annual newsletter; the continuous updating of information on the Lipgene website, and the production of numerous articles in varying health professional and parliamentary magazines. Over the fi ve year project, the dissemination strand has also hosted two conferences each year, where delegates are invited to hear from Lipgene scientists about the latest fi ndings in their area of work. The most recent conferences included a conference in London (November 2007) to communicate the agro-food technology aspects of the project (plant biotechnology and animal nutrition), prior to which a press conference was held, creating worldwide coverage; and a 2-hour satellite meeting in Nottingham, in June 2008.
Lipgene – Diet, genomics, and the metabolic syndrome: 55 an integrated nutrition, agro-food, social and economic analysis 7.7 Demonstration The demonstration project combines knowledge obtained from the activities in nutrition, agro-food technology and consumer understanding to create lipid-modifi ed edible food prototypes with health benefi ts to the metabolic syndrome, which also have acceptable sensory characteristics, and to develop communication routes by which the benefi ts of these modifi cations can encourage consumers to exchange usual foods for these enriched ones. A total of fi ve food products were made with a modifi ed fatty acid profi le. These are: EPA/DHA enriched poultry meat and milk, cheese with reduced saturates and enhanced monounsaturates, two spreads (one 25% fat spread with 500mg EPA and DHA per 20g serving, and one 25% fat spread with 2g ALNA per 20g serving) and a salad oil with 2g ALNA and 500g EPA and DHA per 14g serving. Lipgene scientists also investigated the impact of replacing regular foods with the enriched food prototypes on population intakes of omega-3 PUFAs. This was estimated using dietary data from the UK, the Netherlands and France. As may be expected, it was shown that the availability of food enriched with ALNA, EPA and DHA could help people achieve optimal omega-3 PUFA intakes; however the type of food enriched must be common, everyday foods. With regards to the sensory characteristics of these products, results from sensory testing showed the spreads and oils enriched with omega-3 fatty acids had a shelf-life of 12 weeks, with sensory differences unlikely to be perceived by consumers. Changing the fat composition of the cheese had a signifi cant effect on the sensory properties however the perceived difference is relatively small. Further, enrichment of poultry with EPA and DHA does not compromise the sensory characteristics, even when the meat is reheated. An online consumer study was conducted to evaluate promising communication routes on the metabolic syndrome and the enriched food prototypes. Results showed that the metabolic syndrome is not something consumers reject but rather a preferred communication message. The products also became more acceptable to consumers when the communication was negatively framed e.g. “avoiding the metabolic syndrome” rather than “reaching a positive health situation”.
62 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Thus these foods, if eaten in the context of a healthy, balanced diet and lifestyle, would be expected to have a positive effect on health. Can anything be done to increase the consumption of these foods across Europe? The main factor that determines purchasing patterns are price and taste. The health benefi ts of a product are usually a lower priority. As obesity and coronary heart disease are more prevalent amongst lower income groups it’s important that the price of healthier options is within their reach, so that those who will benefi t most from the foods can afford to buy them. Various options have been considered by researchers in order to achieve this. For example, one option is for the EU to introduce subsidies on these ‘healthier’ foods that cover the extra ingredient costs. This way, the food manufacturers will be able to price their products in line with the conventionally produced foods. Or alternatively the EU could mandate that all animal products available are healthier thus making the market for meats, milks and eggs a much more level paying fi eld. In this instance the public would be picking up the bill for the increased costs, but in this scenario there would be no cheaper, less healthy option. The fi nal option suggested is that those people identifi ed to be most at risk of obesity and other diseases could be encouraged to switch to the healthier brands by targeting subsidies directly at them. In this case, it is those who would benefi t most from a dietary intervention who are receiving an economic incentive to modify their diets. Have initiatives like this been carried out before and have they been successful? Many functional foods are available in supermarkets across Europe but are often sold at higher prices because of the reasons discussed above. In order to encourage those at an increased risk of cardiovascular disease, private heath insurance companies in France and the Netherlands have devised incentives for their members to buy phytosterol spreads. These spreads have been shown to reduce the levels of LDL cholesterol (the bad type) in the blood and thus reduce the risk of developing heart disease. In this instance, a targeted portion of the population are being encouraged to switch to a healthier spread in the hope that it will reduce the chances of them later having to receive treatment for heart problems.
Lipgene – Diet, genomics, and the metabolic syndrome: 63 an integrated nutrition, agro-food, social and economic analysis Appendix 3: Lipgene Publications Human Nutrition Publications Balwierz A, Czech U, Polus A et al. (2008) Human adipose tissue stromal vascular fraction cells differentiate depending on distinct types of media. Cell Proliferation 41: 441-459. Balwierz A, Czech U, Grzybowska-Gałuszka J et al. (2006) Proangiogenne wła´sciwo´sci komórek progenitorowych izolowanych z tkanki tłuszczowej ludzkiej. Prioangiogenic activity of progenitor cells isolated from human adipose tissue. Sympozjum Naukowe pt. “Perspektywy Kardiologii Zapobiegawczej w Polsce”, Warszwa, Polska, 16 grudnia 2006. Czynniki Ryzyka 4 (50): 63 Balwierz A, Czech U, Grzybowska-Gałuszka J et al. (2006) Proangiogenne wła´sciwo´sci komórek progenitorowych izolowanych z tkanki tłuszczowej ludzkiej. Prioangiogenic activity of progenitor cells isolated from human adipose tissue. XI Sympozjum Sekcji Kardiologii Eksperymentalnej Polskiego Towarzystwa Kardiologicznego Komisji Krã¤enia i Oddychania Komitetu Nauk Fizjologicznych PAN Komisji Kardiologii Komitetu Patofi zjologii Klinicznej PAN, Krzy¤owa-Wrocław, Polska, 19-21. pa¤dzierni Kardiologia Polska. 64 (10) S6: 633-634 Balwierz A, Czech U, Grzybowska-Gałuszka J et al. (2005) The infl uence of fatty acids on differentiation of the adipose tissue stromal vascular fraction (SVF) cells. The Third Annual Meeting of the European Stem Cell Therapeutics Excellence Centre (STEC)and The Second Meeting of the Polish Stem Cell Excellence Network, Cracow, Poland, 6-9 October 2005 W: Proceedings of Stem Cell Research: 53 Balwierz A, Czech U, Polus A et al. (2007) Differentiation of human adipose tissue progenitors to adipocytes or endothelial cells using different culture conditions. 42 Meeting of the Polish Biochemical Society, Szczecin, Polska, 18-21 September 2007. Acta Biochimica Polonica 54 (S4): 31 Balwierz A, Czech U, Polus A et al. (2007) Proangiogenic activity of progenitor cells isolated from human adipose tissue. 10th European Nutrition Conference, Paris, France, 10-13 July 2007. Annals of Nutrition & Metabolism 51 (S1): 367 Balwierz A, Czech U, Polus A et al. (2007) Proangiogenic activity of progenitor cells isolated from human adipose tissue. EUROBIOTECH. Biotechnology in Agriculture, Polska, Kraków, 25-27 April 2007. Acta Biochimica Polonica 54 (S1): 6 Balwierz A, Czech U, Grzybowska-Gałuszka J et al. (2006) Proangiogenne wła´sciwo´sci komórek progenitorowych izolowanych z tkanki tłuszczowej ludzkiej. Prioangiogenic activity of progenitor cells isolated from human adipose tissue. Sympozjum Naukowe pt. “Perspektywy Kardiologii Zapobiegawczej w Polsce”, Warszwa, Polska, 16 grudnia 2006. Czynniki Ryzyka 4 (50): 63 Balwierz A, Czech U, Grzybowska-Gałuszka J et al. (2006) Proangiogenne wła´sciwo´sci komórek progenitorowych izolowanych z tkanki tłuszczowej ludzkiej. Prioangiogenic activity of progenitor cells isolated from human adipose tissue. XI Sympozjum Sekcji Kardiologii Eksperymentalnej Polskiego Towarzystwa Kardiologicznego Komisji Krã¤enia i Oddychania Komitetu Nauk Fizjologicznych PAN Komisji Kardiologii Komitetu Patofi zjologii Klinicznej PAN, Krzy¤owa-Wrocław, Polska, 19-21 pa¤dzierni. Kardiologia Polska 64 (10) S6: 633-634 Balwierz A, Czech U, Grzybowska-Gałuszka J et al. (2005) The infl uence of fatty acids on differentiation of the adipose tissue stromal vascular fraction (SVF) cells. The Third Annual Meeting of the European
64 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Stem Cell Therapeutics Excellence Centre (STEC)and The Second Meeting of the Polish Stem Cell Excellence Network, Cracow, Poland, 6-9 October 2005. Proceedings of Stem Cell Research: 53 Balwierz A, Czech U, Polus A et al.(2007) Differentiation of human adipose tissue progenitors to adipocytes or endothelial cells using different culture conditions. 42 Meeting of the Polish Biochemical Society, Szczecin, Polska, 18-21 September 2007. Acta Biochimica Polonica 54 (S4): 31 Balwierz A, Czech U, Polus A et al. (2007) Proangiogenic activity of progenitor cells isolated from human adipose tissue. 10th European Nutrition Conference, Paris, France, 10-13 July 2007. Annals of Nutrition & Metabolism 51 (S1): 367 Balwierz A, Czech U, Polus A, Filipkowski R, Skrzeczyn´ska J, Dudek W, Kaczmarek L, Pryjma J, Dembin´skaKiec´ A (2007) Proangiogenic activity of progenitor cells isolated from human adipose tissue. EUROBIOTECH. Biotechnology in Agriculture, Polska, Kraków, 25-27 April 2007. Acta Biochimica Polonica 54 (S1): 6 Dembin´ska-Kiec´ A (2007) Nutrient Sensors, their polymorphism as the metabolic control and risk for cardiovascular disorders. 42 Meeting of the Polish Biochemical Society, Szczecin, Polska, 18-21 September 2007. Acta Biochimica Polonica 54 (S4): 81 Dembin´ska-Kiec´ A (2007) Nutrigenomics and angiogenesis in obesity. In: Personalized nutrition. Principles and Application. Ed. Kok F, Bouwman L, Desiere F, CRC Press Taylor & Francis Group, London, New York: 89-99. Dembin´ska-Kiec´ A, Polus A, Kiec´-Wilk A et al. (2005) Nutrigenomic as the important determinant of the progenitor cell differentiation factor. Adipogenesis vs angiogenesis. The infl uence of fatty acids on differentiation of the adipose tissue stromal vascular fraction (SVF) cells. The Third Annual Meeting of the European Stem Cell Therapeutics Excellence Centre (STEC)and The Second Meeting of the Polish Stem Cell Excellence Network, Cracow, Poland, 6-9 October 2005. W: Proceedings of Stem Cell Research: 39 Dembin´ska-Kiec´ A & Schmitz G (2007) Effect of beta-carotene and fatty acids on differentiation of preadipocytes. 10th European Nutrition Conference, Paris, France, 10-13 July 2007 Annals of Nutrition & Metabolism 51 (S1):18 Lairon D, López-Miranda J & Williams C (2008) Methodology for studying postprandial lipid metabolism. European Journal of Clinical Nutrition 62:1154 Lopez-Miranda J, Williams C & Lairon D (2007) Dietary, physiological, genetic and pathological infl uences on postprandial lipid metabolism. British Journal of Nutrition 98:458-73. Shaw DI, Hall WL & Williams CM (2005) Metabolic syndrome: what is it and what are the implications? Proceedings of the Nutrition Society 64(3):349-57. Shaw DI, Tierney A, McCarthy S et al. (2008) LIPGENE food exchange model for alteration of dietary fat quantity and quality, in free-living participants with the metabolic syndrome from eight European countries. British Journal of Nutrition 5: 1-19 (epub ahead of print) Zapała B (2008) Human adipose tissue stromal vascular fraction cells differentiate depending on distinct types of media. XIII International Congress of Histochemistry and Cytochemistry, ICHC2008 “Imaging of Cell Dynamics”, Gdan´sk, Poland, 23-27 August 2008. Folia Histochem Cytobiol 46(S2): s93
Lipgene – Diet, genomics, and the metabolic syndrome: 65 an integrated nutrition, agro-food, social and economic analysis Abstracts Balwierz A, Czech U, Grzybowska-Gałuszka J et al. (2006) Angiogenic potential of progenitor cells isolated from human adipose tissue. Third European Nutrigenomics Conference, Oxford, UK, 12-15 September 2006. Abstract Book: 53 Balwierz A, Czech U, Polus A et al. (2008) Human adipose tissue stromal vascular fraction cells differentiate depending on distinct types of media. Third Integrative Physiology Post-Graduate Students Conference, Aberdeen, UK, 22-23 May 2008 Abstract Book: 10 Balwierz A, Czech U, Polus A et al. (2007) Proangiogenic activity of progenitor cells isolated from human adipose tissue. 15th Symposium of Jagiellonian Medical Research Centre, Poland, Krakow, 9-12 May 2007 Abstract Book: 27-28 Balwierz A, Czech U, Polus A et al. (2007) Proangiogenic activity of progenitor cells isolated from human adipose tissue. Third International Meeting on Angiogenesis VU University Medical Center, Amsterdam, The Netherlands, 1-3 March 2007 Abstract Book: 88 Balwierz A, Czech U, Grzybowska-Gałuszka J et al. (2006) Angiogenic potential of progenitor cells isolated from human adipose tissue. Third European Nutrigenomics Conference, Oxford, UK, 12-15 September 2006. Abstract Book: 53 Balwierz A, Czech U, Polus A et al. (2008) Human adipose tissue stromal vascular fraction cells differentiate depending on distinct types of media. Third Integrative Physiology Post-Graduate Students Conference, Aberdeen, UK, 22-23 May 2008 Abstract Book: 10 Balwierz A, Czech U, Polus A et al. (2007) Proangiogenic activity of progenitor cells isolated from human adipose tissue. 15th Symposium of Jagiellonian Medical Research Centre, Poland, Krakow, 9-12 May 2007 Abstract Book: 27-28 Balwierz A, Czech U, Polus A et al. (2007) Proangiogenic activity of progenitor cells isolated from human adipose tissue. Third International Meeting on Angiogenesis VU University Medical Center, Amsterdam, The Netherlands, 1-3 March 2007. Abstract Book: 88 Bêtkowska-Korpała B, Karpowicz A, Gierowski JK et al. (2007) Coping with Stress and Cardiovascular Disease in Obese People. Central European Meeting on Hypertension and Cardiovascular Disease Prevention, Kraków. Poland, 11-13 October 2007. Kidney & Blood Press Research 30: 375 Bêtkowska-Korpała B, Karpowicz A, Gierowski JK et al. (2007) Style radzenia sobie ze stresem a choroby układu krã¤enia u osób otyłych. (Coping with stress and cardiovascular disease in obese people.) Central European Meeting on Hypertension and Cardiovascular Disease Prevention, Kraków. Poland, 11-13 October 2007 Nadci è nienie T ê tnicze 11 (5): 471 Castillo-Roldán I, García A, Góemz P et al. (2008) Effect of type of fat in the diet on the adipose tissue markers in patiens with metabolic syndrome. XXI Congreso Nacional de la Sociedad Española de Arteriosclerosis 2008. Cruz-Teno C, Jiménez-Gómez Y, Fuentes F et al. (2008) Diet, oxidative stress and metabolic syndrome. XXI Congreso Nacional de la Sociedad Española de Arteriosclerosis
66 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Dembin´ska-Kiec´ A (2007) Nutrient Sensors, their polymorphism as the metabolic control and risk for cardiovascular disorders. 42 Meeting of the Polish Biochemical Society, Szczecin, Polska, 18-21 September 2007 Acta Biochimica Polonica 54 (S4): 81 Dembin´ska-Kiec´ A (2005) Nutrigenomika - nowa dziedzina badan´ medycyny prewencyjnej w kardiologii. X Sympozjum Sekcji Kardiologii eksperymentalnej Polskiego Towarzystwa Kardiologicznego Komisji Krã¤enia i Oddychania Komitetu Nauk Fizjologicznych PAN oraz Komisji Kardiologii Komitetu Patofi zjologii Klinicznej PAN, POZNAÜ-KIEKRZ 20-22 Pa¤dziernik 2005 Kardiologia Polska 63 (SII): 390-391 Dembin´ska-Kiec´ A, Hartwich J, Malczewska-Malec M et al. (2008) The effect of the LC n-3 PUFA dietary intervention on the proatherogenic LDL phenotype and ischemia-modifi ed albumin (IMA) related to posprandial response. The LIPGENE study. Oxygen Club of California 2008 “Oxidants and Antioxidants in Biology”, Santa Barbara, USA, 12-15 March 2008, Abstract Book:71 Dembin´ska-Kiec´ A, Hartwich J, Malczewska-Malec M et al. (2008) The effect of the plasma n-3/n-6 PUFA ratio on the post-dietary LDL phenotype transformation in patients with metabolic syndrome. The LIPGENE study. Fourth Santorini Conference Biologie Prospective 2008 “Functional Genomics towards Personalized Health Care”, Santorini, Greece, 21-23 September 2008 Clin Chem Lab Med 46 (8s): A112 Gómez MJ, Castillo-Roldán I, Fuentes FJ et al. (2008) Effect of type of dietary fat on the postprandial endothelial function in patients with metabolic syndrome. XXI Congreso Nacional de la Sociedad Española de Arteriosclerosis Hartwich J, Malczewska-Malec M, Partyka Ł et al. (2008) The effect of the post-dietary plasma n-3/n-6 PUFA ratio on the transformation of LDL phenotype, postprandial state lipoprotein and Ischemia Modifi ed Albumin. The LIPGENE Study. 5th European Nutrigenomics Conference, NUGOWEEK 2008, Potsdam, 2-5 September 2008, Abstract Book:155 Hartwich J, Malczewska-Malec M, Partyka Ł et al. (2008) The effect of post-dietary plasma n-3/n-PUFA ratio on transformation of proatherogenic LDL phenotype, postprandial state lipoprotein and ischemia modifi ed albumin. The LIPGENE study. 49th International Conference on the Bioscience of Lipids, Maastricht, the Netherlands, 26-30 August 2008 Chemistry and Physics of Lipids 154S: S47 Hartwich J, Malczewska-Malec M, Partyka Ł et al. (2008) The effect of the plasma n-3/n-6 PUFA ratio on the dietary LDL phenotype transformation and ischemia modifi ed albumin (IMA) related to postprandial response. The LIPGENE study, Fourth Santorini Conference Biologie Prospective 2008 “Functional Genomics towards Personalized Health Care”, Santorini, Greece, 21-23 September 2008 Clin Chem Lab Med 46 (8s): A131 Jiménez-Gómez Y, Delgado J, Ruano J et al. (2008) Postprandial oxidative status after the intake of diets with different fat composition in patients with metabolic syndrome. XXI Congreso Nacional de la Sociedad Española de Arteriosclerosis Malczewska-Malec M, Leszczyn´ska-Gołãbek I, Partyka Ł et al. (2008) The leptin to adiponectin ratio after dietary intervention in patients with metabolic syndrome. 5th European Nutrigenomics Conference, NUGOWEEK 2008, Potsdam, 2-5 September 2008, Abstract Book:156
Lipgene – Diet, genomics, and the metabolic syndrome: 67 an integrated nutrition, agro-food, social and economic analysis Malczewska-Malec M, Patyka Ł, Siedlecka D et al. (2008) The infl uence of dietary fat on leptin to adiponectin ratio in patient with metabolic syndrome. 8th Meeting of France - New EU Members, 16th JMRC Symposium, 5-7 June, Kraków, Poland, 2008 Abstract Book: 66 Marín C, Gómez MJ, Delgado J et al. (2008) XXI Congreso Nacional de la Sociedad Española de Arteriosclerosis. Dietary fat and postprandial lipoprotein metabolism in metabolic síndrome. XXI Congreso Nacional de la Sociedad Española de Arteriosclerosis Polus A, Mikołajczyk M, Szota J et al. (2007) Fatty acids and endothelial cells differentiation. 15th Symposium of Jagiellonian Medical Research Centre, Poland, Krakow, 9-12 May 2007 Abstract Book: 44-45. Shaw DI, Tierney A, McCarthy S et al. (2008) The LIPGENE food-exchange model: a tool to enable investigation of four diets distinct in fatty acid composition. Proceedings of the Nutrition Society E86 (epub ahead of print) Siedlecka D, Hartwich J, Góralska J et al.(2007) Wpływ kwasów tłuszczowych na parametry lipidowe mierzone na czczo oraz w przebiegu doustnego testu tolerancji lipidów (DTTL). (Infl uence of different fatty acids on fasting lipid parameters and during oral lipid tolerance test (OLTT)). Zjazd Polskiego Towarzystwa Badan´ Nad Otyłoèciã, Poznan´, Polska, 27-29 wrzeènia, 2007 Endokrynologia, Otyło èú i Zaburzenia Przemiany Materii 3 (2):68-69 Siedlecka-Wnêk D, Malczewska-Malec M, Leszczyn´ska-Gołãbek I et al. (2008) Dietary habits in Polish patients with metabolic syndrome. Central European Congress of Life Sciences EUROBIOTECH 2008, Krakow, 17-19 October 2008 Acta Biochimica Polonica 55 (S4):104 Siedlecka-Wnêk D, Malczewska-Malec M, Leszczyn´ska-Gołãbek I et al. (2008) The infl uence of dietary fat on leptin to adiponectin ratio in patient with metabolic syndrome. COST Action 926 Conference “Benefi ts and Risks of Bioactive Plant Compounds”, Kraków, Poland, 27-28 March 2008 Acta Biocheimica Polonica 55 (S1/21): 1,38 Wybran´ska I, Malczewska-Malec M, Partyka Ł et al. (2007) Evaluation of genetic predisposition to insulin resistance by nutrient-induced insulin output ratio (NIOR). 2nd International Symposium Integrated Biomarkers in Cardiovascular Diseases, Germany, Berlin, 21-23 June, 2007, Abstract Book: 44 Book Chapters López-Miranda J, Pérez-Martínez P & Pérez-Jiménez F (2006). Health benefi ts of monounsaturated fatty acids (PUFAs). In Improving the fat content of foods P71-106. [J Buttriss and C Williams, Editors]. Cambridge: Woodhead Publishing Limited. Minihane AM & Lovegrove JA (2006). Health benefi ts of polyunsaturated fatty acids (PUFAs). In Improving the fat content of foods P107-40. [J Buttriss and C Williams, Editors]. Cambridge: Woodhead Publishing Limited. Shaw DI, Hall WL & Williams CM (2006). Dietary fatty acids, insulin resistance and diabetes. In Improving the fat content of foods P24-48. [J Buttriss and C Williams, Editors]. Cambridge: Woodhead Publishing Limited.
68 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Manuscript In Preparation Hartwich J, Leszczynska-Golabek I, Kiec´-Wilk B et al. Lipoprotein profi le, Ischemia Modifi ed Albumin and LDL density in postprandial lipemia - LIPGENE study. Submitted to Nutrition, Metabolism & Cardiovascular Diseases. Hartwich J, Malczewska-Malec M, Partyka L et al. The effect of the plasma n-3/n-6 polyunsaturated fatty acid ratio on the dietary LDL phenotype transformation - insights from the LIPGENE study. Submitted to Clinical Nutrition. Hartwich J, Leszczynska-Golabek I, Siedlecka D et al. Analysis of gene polymorphisms related to LDL density. LIPGENE Study.Draft paper. Jiménez-Gómez Y, Marin C, Pérez-Martínez P, Hartwich J, Malczewska-Malec M, Gołabek I, Kiec´-Wilk B, Cruz-Teno C, Gomez-Luna MJ, Defoort C, Perez-Jimenez F, Roche H & José López-Miranda J (2008) The quality and quantity of fat in the diet infl uences the postprandial lipoprotein response in patients with metabolic syndrome. Journal of the American Medical Association Plant Biotechnology Graham IA, Larson T & Napier JA (2007) Rational metabolic engineering of transgenic plants for biosynthesis of omega-3 polyunsaturates. Current opinions in Biotechnology 18(2):142-7. Sayanova O, Haslam R, Guschina I et al. (2006). A bifunctional Delta12,Delta15-desaturase from Acanthamoeba castellanii directs the synthesis of highly unusual n-1 series unsaturated fatty acids. Journal of Biological Chemistry 281(48):36533-41. Sayanova O, Haslam R, Qi B et al. (2006). The alternative pathway C20 Delta8-desaturase from the non-photosynthetic organism Acanthamoeba castellanii is an atypical cytochrome b5-fusion desaturase. FEBS Letters 580(8):1946-52. Venegas-Calerón M, Beaudoin F, Sayanova O et al. (2007). Co-transcribed genes for long chain polyunsaturated fatty acid biosynthesis in the protozoon Perkinsus marinus include a plant-like FAE1 3-ketoacyl coenzyme A synthase. Journal of Biological Chemistry 282(5):2996-3003. Animal Nutrition Bernard L, Leroux C & Chilliard Y (2008) Expression and nutritional regulation of lipogenic genes in the ruminant lactating mammary gland. Advances in Experimental Medicine and Biology 606:67-108. Chilliard Y, Glasser F, Ferlay A et al. (2007) Diet, rumen biohydrogenation, cow and goat milk fat nutritional quality: a review. European Journal of Lipid Science and Technology 109: 828-855 Chilliard Y, Rouel J, Ferlay A et al. (2006) Optimising goat’s milk and cheese fatty acid composition. Chapter 12 in “Improving the fat content of foods” (C. Williams and J. Buttriss, Eds), Woodhead Publishing Ltd. (Cambridge, UK): p.281-312. Devillard E, McIntosh FM, Paillard D et al. Differences between human subjects in the composition of the faecal bacterial community and faecal metabolism of linoleic acid. Microbiology. In press. Gibbs RA, Givens DI & Rymer C (2007) The effect of age and gender oncurrent and potential intakes of very long chain n-3 polyunsaturated fatty acids from oil-rich fi sh and animal derived foods. Proceedings of the British Society of Animal Science p009.
Lipgene – Diet, genomics, and the metabolic syndrome: 69 an integrated nutrition, agro-food, social and economic analysis Gibbs RA, Rymer C & Givens DI (2007) Effect of dietary source of very long chain n-3 polyunsaturated fatty acids on their concentrations in the edible tissues of the chicken. Proceedings of the British Society of Animal Science, p016. Gibbs RA, Rymer C & Givens DI (2007) Effect of dietary source of very long chain n-3 polyunsaturated fatty acids on the EPA and DHA concentrations of edible chicken tissues. Proceedings of the Summer Meeting of the Nutrition Society, paper OC59, p84 Givens DI (2005) The role of animal nutrition in improving the nutritive value of animal-derived foods in relation to chronic disease. Proceedings of the Nutrition Society 64: 1-8. Givens DI (2007). Animal nutrition and lipids in animal products. Annals of Nutrition & Metabolism 51 (suppl 1), 34. Givens DI (2008). Polyunsaturated fatty acids: are you getting enough of the right type? Biologist 55: 23-27. Givens DI (2008). Impact on CVD risk of modifying milk fat to decrease intake of saturated fatty acids and increase intake of cis-monounsaturates. Proceedings of the Nutrition Society 67: 419-427. Givens DI (2008) Session 4: Challenges facing the food industry in innovating for health. Impact on CVD risk of modifying milk fat to decrease intake of SFA and increase intake of cis-MUFA. Proceedings of the Nutrition Society 67(4):419-27. Givens DI & Gibbs RA (2006) Very Long Chain N-3 Polyunsaturated Fatty Acids in the Food Chain in the UK and the Potential of Animal-Derived Foods to Increase Intake. Feedinfo News Service Scientifi c Reviews. July 2006. Available from URL: http://www.feedinfo.com.” Givens DI & Gibbs RA (2006) Very long chain n-3 polyunsaturated fatty acids in the food chain in the UK and the potential of animal-derived foods to increase intake. Nutrition Bulletin 31: 104–110. Givens DI & Gibbs RA (2008). Current intakes of EPA and DHA in European populations and the potential of animal-derived foods to increase them. Proceedings of the Nutrition Society 67: 273-280. Givens DI, Kliem KA & Gibbs RA (2006) The role of meat as a source of n-3 polyunsaturated fatty acids in the human diet. Meat Science 74: 209-218. Givens DI & Shingfi eld KJ (2004) Food derived from animals: the impact of animal nutrition on their nutritive value and ability to sustain long-term health. Nutrition Bulletin 29:325-332. Givens DI & Shingfi eld KJ (2006) Optimising dairy milk fatty acid composition. In: Improving the fat content of foods (Ed. C.M. Williams and J. Buttriss), Woodhead Publishing Ltd., Cambridge, UK, pp. 252280. Kliem KE, Morgan R, Humphries DJ et al. Effect of replacing grass silage with maize silage in the diet on bovine milk fatty acid composition. Animal. In press. McIntosh FM, Shingfi eld KJ, Devillard E et al. Mechanism of formation of conjugated linoleic acids and vaccenic acid in human faecal suspensions and pure cultures of intestinal bacteria. Microbiology. In press.
70 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Ollier S (2007) Mammary transcriptome analysis of food-deprived lactating goats highlights genes involved in milk secretion and programmed cell death. Journal of Nutrition 137:560-7. Ollier S, Leroux C, de la Foye A et al. (2008) Whole Rapeseeds or Sunfl ower Oil Supplementations in High Forage or High Concentrate Diets Affect Goat Milk Yield and Composition and Global Mammary Gene Expression Profi le without Major Changes in mRNA Levels. Submitted for publication Paillard D, McKain N, Rincon MT et al. (2007) Quantifi cation of ruminal Clostridium proteoclasticum by real-time PCR using a molecular beacon approach. Journal of Applied Microbiology 103:1251-1261. Rymer C (2008) Effect of different inclusion rates of fi sh oil and vitamin E in broiler diets on the long chain n-3 polyunsaturated fatty acid content and sensory analysis of chicken meat. Presented at a meeting of British Society for Animal Science, 2008. Rymer C & Givens DI (2005) n-3 fatty acid enrichment of edible tissue of poultry: A review. Lipids 40:121-130. Rymer C & Givens DI (2006) Effect of species and genotype on the effi ciency of enrichment of poultry meat with n-3 polyunsaturated fatty acids. Lipids 41: 445-451. Rymer C & Givens DI (2007) Effect of dietary source of very long chain n-3 polyunsaturated fatty acids in poultry diets on the oxidative stability of chicken meat. Proceedings of the British Society of Animal Science, p017. Shingfi eld KJ, Chilliard Y, Toivonen V et al. (2008). Trans fatty acids and bioactive lipids in ruminant milk. In: Bioactive components of milk, Advances in Experimental Medicine and Biology, Volume 606 (Ed. Z. Bösze), Springer, New York, NY. pp. 3-65. Shingfi eld KJ, Chilliard Y, Toivonen V et al. (2008) Trans fatty acids and bioactive lipids in ruminant milk. Advances in Experimental Medicine and Biology 606:3-65. Wallace RJ, McKain N, Shingfi eld KJ et al. (2007) Isomers of conjugated linoleic acids are synthesized via different mechanisms in ruminal digesta and bacteria. Journal of Lipid Research 48: 2247-2254. Posters: Chilliard Y, Ollier S, Rouel J et al. (2006) Milk fatty acid profi le in goats receiving high forage or high concentrate diets supplemented, or not, with either whole rapeseeds or sunfl ower oil. Page 296 In: Book of Abstracts, 57th Annual Meeting of European Association for Animal Production, Antalya, Turkey, 17-20 September 2006, Wageningen Acad. Publ. (NL). Ollier S, Robert-Granié C, Bes S et al. (2006). Impact of nutrition on mammary transcriptome and its interaction with the CSN1S1 genotype in lactating goats. Page 49 In: Book of Abstracts, 57th Annual Meeting of European Association for Animal Production, Antalya, Turkey, 17-20 September 2006, Wageningen Acad. Publ. (NL). Economics Fry J & Finley W (2005) The prevalence and costs of obesity. Proceedings of the Nutrition Society 64(3): 359-62.
Lipgene – Diet, genomics, and the metabolic syndrome: 71 an integrated nutrition, agro-food, social and economic analysis Consumer Understanding and Awareness de Almeida MDV, Pinhao S, Stewart-Knox BJ et al. (2006) An overview of fi ndings from a six-country European survey on consumer attitudes to the metabolic syndrome, genetics in nutrition and potential agro-food technologies. Nutrition Bulletin 31:239-246. de Almeida MDV, Pinhao S, Stewart-Knox BJ et al. (2006) A six-country survey on consumer attitudes to the metabolic syndrome, genetics in nutrition and potential agro-food technologies: questionnaire design methodology. Nutrition Bulletin 31:138-144. Stewart-Knox BJ (2005) Psycho-social underpinnings of metabolic syndrome. Bulletin of the British Nutrition Society 64(3). Stewart-Knox BJ, Bunting BP, Gilpin S et al. (2008) Attitudes toward genetic testing and personalised nutrition in a representative sample of European consumers. British Journal of Nutrition (on-line). Published Abstracts de Almeida MDV, Pinhao S, Parr H et al. (2007) Consumer attitudes on nutrition and health. Annals of Nutrition & Metabolism 51:48. de Almeida MDV, Pinhão S, Parr H et al. (2007) Medidas e barreiras para a adopção de hábitos alimentares em função de situações de saúde relacionadas com a síndrome metabólica. Alimentação Humana 13: 22. Parr H, Pinhão S, Stewart-Knox B et al. (2007) Consumer Perceptions of functional foods: Results from a qualitative study. ILSI 2007.Symposium on functional foods in Europe – International developments in science and health claims, 9-11 May 2007, Malta. Available at: http://europe.ilsi.org/events/past/ postersffsympo.htm Parr H, Stewart-Knox B, Bunting B et al. (in press) Dietary habits and the metabolic syndrome in middle-aged Europeans. Proceedings of the Nutrition Society. Parr HJ, Stewart-Knox B, Pinhao S et al. (2006) Stakeholder opinion of interventions to prevent and treat obesity. Public Health Nutrition 9:263a. Pinhao S, Parr HJ, Stewart-Knox B et al. (2006) Consumer views on functional and genetically modifi ed foods. Public Health Nutrition 9:263b. Pinhão S, Parr H, Stewart-Knox B et al. (2007) Relação entre a percepção de várias condições relacionadas com a síndrome metabólica e hábitos alimentares e de actividade física num grupo de portugueses e ingleses. Alimentação Humana 13:6. Pinhão S, Parr H, Stewart-Knox B et al. (2007). Síndrome Metabólica e Novas tecnologias agroalimentares: uma análise qualitativa de percepções de consumidores portugueses. Alimentação Humana 13:21. Stewart-Knox B, Bunting B, Parr HJ et al. (2007) Metabolic Syndrome and Dietary health promotion needs in European consumers. 2007 Northern Ireland Branch Annual Conference. Conference Proceddings. Available at: http://www.bps.org.uk/conferences-and-events/proceedings/proceedings_ home.cfm?&ResultsType=Abstracts&ResultSet_ID=1132&FormDisplayMode=view&frmShowSelected =true&localAction=details
78 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis Dissemination British Nutrition Foundation Prof. Judith Buttriss Britsh Nutrition Foundation 52-54 High Holborn London WC1 V6RQ, United Kingdom Ph: + 44 2074 046 504 Fax: + 44 2074 046 747 Email: [email protected]g.uk Economic Science LMC International Dr. James Fry LMC International Limited 14-16 George Street Oxford OX1 2AF, United Kingdom Ph: + 44 1865 791 737 Fax: + 44 1865 791 739 Email: [email protected] Demonstration MTT Agrifoods Research, Finland Dr. Kevin Shingfi eld Animal Production Research / Animal Nutrition MTT Agrifood Research Finland H-House, Fin-31600 Jokioinen Finland Ph: +358 3 4188 3694 Fax: + 358 3 4188 3661 Email: kevin.shingfi eld@mtt.fi University College Dublin, Ireland Prof. Michael Gibney Institute of Food & Health University College Dublin Belfi eld, Dublin 4, Ireland. Ph: + 353 1 617 7801 Fax: + 353 1 716 1147 Email: mike.g[email protected] Unilever Dr. Maeve Cosgrove Unilever Food and Health Research Institute Olivier van Noortlaan 120, PO Box 114, 3130 AC Vlaardingen, Netherlands Email: [email protected]
Lipgene – Diet, genomics, and the metabolic syndrome: 79 an integrated nutrition, agro-food, social and economic analysis EU Contact Uta Faure European Commission Directorate General for Research Unit E3: Food – Health – Well-being Square de Meeus 8 SDME 8/8, B-1049 Brussels, Belgium Ph: +32.2.296.33.34 Fax: +32.2.296.43.22 E-mail: [email protected] Scientifi c Offi ce Dr. Anne Nugent Institute of Food & Health Institute of Food & Health University College Dublin Belfi eld, Dublin 4, Ireland. Ph: + 353 1 716 7311 Fax: + 353 1 716 1147 E-mail: anne.nug[email protected] Administrative Offi ce Mrs. Jo. Gibney Institute of Food & Health University College Dublin Belfi eld, Dublin 4, Ireland. Ph: + 353 1 716 7311 Fax: + 353 1 716 1147 Email: jo.g[email protected]
80 Lipgene – Diet, genomics, and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis