Accelerometer-Based Sedentary Time, Physical Activity, and Serum Metabolome in Young Men

This is a self-archived version of an original article. This version may differ from the original in pagination and typographic details. Author(s): Title: Year: Version: Copyright: Rights: Rights url: Please cite the original version: CC BY 4.0 https://creativecommons.org/licenses/by/4.0/ Accelerometer-Based Sedentary Time, Physical Activity, and Serum Metabolome in Young Men © 2022 by the authors. Licensee MDPI, Basel, Switzerland. Published version Vaara, Jani P.; Kyröläinen, Heikki; Vasankari, Tommi; Kainulainen, Heikki; Raitanen, Jani; Kujala, Urho M. Vaara, J. P., Kyröläinen, H., Vasankari, T., Kainulainen, H., Raitanen, J., & Kujala, U. M. (2022). Accelerometer-Based Sedentary Time, Physical Activity, and Serum Metabolome in Young Men. Metabolites, 12(8), 700. https://doi.org/10.3390/metabo12080700 2022 Citation: Vaara, J.P.; Kyröläinen, H.; Vasankari, T.; Kainulainen, H.; Raitanen, J.; Kujala, U.M. Accelerometer-Based Sedentary Time, Physical Activity, and Serum Metabolome in Young Men. Metabolites 2022,12, 700. https:// doi.org/10.3390/metabo12080700 Academic Editor: Harald C. Köfeler Received: 31 May 2022 Accepted: 21 July 2022 Published: 27 July 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). metabolites H OH OH Article Accelerometer-Based Sedentary Time, Physical Activity, and Serum Metabolome in Young Men Jani P. Vaara 1,* , Heikki Kyröläinen 2, Tommi Vasankari 3,4 , Heikki Kainulainen 2, Jani Raitanen 3,5,6 and Urho M Kujala 2 1Department of Leadership and Military Pedagogy, National Defence University, 00861 Helsinki, Finland 2Faculty of Sport and Health Science, University of Jyväskylä, 40014 Jyväskylän, Finland; [email protected] (H.K.); [email protected] (H.K.); ur[email protected] (U.M.K.) 3UKK-Institute for Health Promotion Research, 33500 Tampere, Finland; [email protected] (T.V.); [email protected] (J.R.) 4Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland 5Faculty of Social Sciences (Health Sciences), Tampere University, 33100 Tampere, Finland 6Special Services Unit, Finnish Institute for Health and Welfare, 00271 Helsinki, Finland *Correspondence: [email protected]; Tel.: +358-299530432 Abstract: Physical activity (PA) has been shown to associate with many health benefits but studies with metabolome-wide associations with PA are still lacking. Metabolome studies may deepen the mechanistic understanding of PA on the metabolic pathways related to health outcomes. The aim of the present study was to study the association of accelerometer based sedentary time (SB) and PA with metabolome measures. SB and PA were measured by a hip-worn accelerometer in 314 young adult men (age: mean 28, standard deviation 7 years). Metabolome was analyzed from fasting serum samples consisting of 66 metabolome measures (nuclear magnetic resonance-based metabolomics). The associations were analyzed using a single and compositional approach with regression analysis. The compositional analysis revealed that 4 metabolome variables were significantly ( γ : 0.32–0.44, p ≤ 0.002), and 13 variables with a trend towards significance (p< 0.05), associated with SB with varying metabolic pathways. Trends towards significant associations (p< 0.05) were observed with 5 variables with moderate-to-vigorous and 1 variable with light intensity PA with varying metabolic pathways. The present study revealed possible mechanistic pathways relevant for the interaction between especially SB but also PA of moderate-to-vigorous intensity with ketone bodies and amino acid concentration related to exercised-induced energy production and lipid metabolism. Keywords: objective physical activity; sedentary time; body composition; metabolomics; cardiovascular risk factors 1. Introduction Physical activity associates with many health benefits including cardiometabolic outcomes in adults and adolescents [ 1 , 2 ]. Often studies have concentrated on specific health outcomes, such as blood pressure or cholesterol concentrations. Recently, analyses of metabolome pattern have enabled to focus on metabolic outcomes and their pathways with broader aspects to elucidate deeper mechanistic insight. This is important since physical activity induces many physiological responses that together may be beneficial for overall health of an individual. Therefore, the assessment of metabolome-wide associations with physical activity may deepen our mechanistic understanding of the metabolic pathways related to health [3]. Although acute physical activity bouts have been shown to induce molecular responses in metabolism [ 4 ] and chronic physical activity to associate with health [ 5 ], only a few previous studies have investigated the relationships between physical activity and metabolomics. These previous metabolome studies have shown physical activity to associate with fatty acid Metabolites 2022,12, 700. https://doi.org/10.3390/metabo12080700 https://www.mdpi.com/journal/metabolites Metabolites 2022,12, 700 2 of 13 profile, amino acids, carbohydrate metabolism, and inflammatory glycoproteins [ 6 – 11 ] with one study in adolescents showing no significant associations [ 12 ]. Besides these studies, there are fewer of those that have assessed metabolomeand accelerometer-based physical activity and sedentary time [ 7 , 10 , 13 ]. Accelerometer-based measures may allow more precise estimates of especially light intensity activity and sedentary time compared to the self-report method, known to include precision bias such as over-reporting or recall bias. Therefore, the purpose of the present study was to study the associations of accelerometerbased sedentary time and physical activity with targeted serum metabolome in a focused study sample consisting of young healthy adult men. 2. Results The baseline characteristics including sedentary time and physical activity of the participants are presented in Table 1. Supplementary Table S1 describes the mean, standard deviation, and 95% confidence interval for serum metabolome outcomes. Table 1. Demographic and baseline characteristics of the study population (n= 314). Characteristics Mean (Standard Deviation) 95% Confidence Interval Age in years 28.2 (7.3) 27.4–29.0 Smokers, n(%) 75 (24.0) 19.6–29.0 * Sedentary time Total sedentary time (min) 707.6 (127.3) 693.5–721.8 Total sedentary time (relative to accelerometer wear time, %) 77.6 (8.0) 76.8–78.5 Physical activity (min) Light Activity (1.5–3 MET) (min) 119.8 (47.1) 114.6–125.1 Moderate Activity (3–6 MET) (min) 77.8 (32.4) 74.2–81.4 Vigorous Activity (>6 MET) (min) 4.4 (6.3) 3.7–5.1 Moderate-to-Vigorous Activity (≥3 MET) (min) 82.1 (34.0) 78.4–85.9 Physical activity relative to accelerometer wear time (%) Light Activity (1.5–3 MET) (%) 13.2 (5.1) 12.7–13.8 Moderate Activity (3–6 MET) (%) 8.6 (3.6) 8.2–9.0 Vigorous Activity (>6 MET) (%) 0.48 (0.67) 0.41–0.56 Moderate-to-Vigorous Activity (≥3 MET) (%) 9.1 (3.8) 8.7–9.5 * The Wilson score method without continuity correction (Newcombe RG (1998) Two-sided confidence intervals for the single proportion: Comparison of seven methods. Statistics in Medicine, 17, 857–872.). MET = metabolic equivalent. The linear regression analysis is shown in Table 2and the compositional analysis in Table 3with the adjustments of age, education, smoking, alcohol, and nutrition. The level of statistical significance was found with a Bonferroni-corrected p-value of ≤ 0.002. The compositional analysis revealed that four metabolome variables (IDL concentration in TG, LDL concentration in TG, Acetoacetate, 3-hydroxybuturate) were significantly (p ≤ 0.002) positively associated with SB with varying metabolic pathways (Table 3). In addition, 13 (Very small VLDL, IDL, Large HDL, HDL diameter, ApoB, ApoB Apo A1 -ratio, HDL-C, HDL2-C, Unsaturation degree, Saturated FA ratio, Glycerol, Leucine, Valine) variables with a trend towards significance (p< 0.05) were positively associated with SB with varying metabolic pathways. The trend towards significant associations (p< 0.05) was also observed with five variables related to HDL metabolism (HDL-C, HDL2-C, ApoA1, Medium HDL, Large HDL) with moderate-to-vigorous physical activity, and one variable (lactate) with light intensity physical activity (p< 0.05) (Table 3). Further adjustments for either body fat percentage or aerobic fitness attenuated the associations mostly to non-significant ( Tables S3 and S4 ). Moreover, Supplementary Table S2 demonstrates the associations between the accumulated physical activity intensities and serum metabolome biomarkers adjusted for age only. Metabolites 2022,12, 700 3 of 13 Table 2. Standardized single regression coefficients ( β ) of sedentary time and physical activity intensities with their 95% confidence intervals (CI) from age, education, smoking, alcohol, and nutrition-adjusted linear regression models for serum metabolome. Bonferroni-corrected p-value of ≤ 0.002 was set as the level for statistical significance, which corresponds to a p-value of less than 0.05. Sedentary Time Light Intensity Physical Activity Moderate-toVigorous Physical Activity Metabolome Measure β(95% CI) p-Value β(95% CI) p-Value β(95% CI) p-Value Lipoprotein particle concentration Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Extremely large VLDL 0.07 (−0.03; 0.16) 0.191 −0.07 (−0.16; 0.03) 0.150 −0.05 (−0.16; 0.06) 0.345 Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Very large VLDL 0.09 (−0.02; 0.20) 0.111 −0.10 (−0.21; 0.02) 0.089 −0.06 (−0.16; 0.05) 0.285 * Large VLDL 0.06 (−0.06; 0.17) 0.342 −0.06 (−0.19; 0.06) 0.314 −0.06 (−0.17; 0.05) 0.296 Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Medium VLDL 0.08 (−0.04; 0.21) 0.196 −0.09 (−0.21; 0.04) 0.188 −0.08 (−0.21; 0.04) 0.196 Small VLDL 0.08 (−0.02; 0.18) 0.099 −0.09 (−0.19; 0.01) 0.085 −0.06 (−0.16; 0.04) 0.225 Very small VLDL 0.12 (0.02; 0.22) 0.021 −0.11 (−0.21; 0.00) 0.043 −0.11 (−0.21; −0.01) 0.028 IDL 0.11 (0.01; 0.21) 0.040 −0.09 (−0.19; 0.02) 0.108 −0.11 (−0.22; −0.01) 0.027 Large LDL 0.10 (−0.00; 0.21) 0.055 −0.08 (−0.19; 0.03) 0.140 −0.11 (−0.21; −0.01) 0.037 Medium LDL 0.10 (−0.00; 0.20) 0.059 −0.08 (−0.19; 0.03) 0.142 −0.11 (−0.21; −0.00) 0.042 Small LDL 0.10 (−0.01; 0.20) 0.072 −0.08 (−0.19; 0.03) 0.144 −0.10 (−0.20; 0.005) 0.062 Very large HDL −0.09 (−0.20; 0.02) 0.128 0.06 (−0.06; 0.17) 0.333 0.11 (−0.00; 0.21) 0.055 Large HDL −0.13 (−0.24; −0.02) 0.022 0.09 (−0.02; 0.21) 0.112 0.15 (0.04; 0.26) 0.006 Medium HDL −0.08 (−0.19; 0.03) 0.147 0.06 (−0.05; 0.18) 0.298 0.09 (−0.02; 0.20) 0.094 Small HDL 0.04 (−0.07; 0.15) 0.487 −0.03 (−0.15; 0.08) 0.582 −0.04 (−0.15; 0.07) 0.462 Lipoprotein particle size VLDL diameter 0.05 (−0.06; 0.16) 0.401 −0.06 (−0.18; 0.06) 0.305 −0.02 (−0.14; 0.09) 0.669 LDL diameter −0.02 (−0.13; 0.09) 0.759 0.04 (−0.07; 0.16) 0.443 −0.02 (−0.13; 0.09) 0.728 HDL diameter −0.11 (−0.22; −0.01) 0.040 0.08 (−0.03; 0.20) 0.148 0.13 (0.02; 0.24) 0.016 Apolipoproteins ApoA1 −0.09 (−0.20; 0.02) 0.120 0.05 (−0.06; 0.17) 0.372 0.12 (0.01; 0.23) 0.037 ApoB 0.10 (−0.00; 0.21) 0.056 −0.10 (−0.20; 0.01) 0.081 −0.09 (−0.19; 0.01) 0.085 ApoB ApoA1 ratio 0.14 (0.03; 0.24) 0.012 −0.12 (−0.23; −0.01) 0.034 −0.13 (−0.24; −0.03) 0.012 Triglycerides Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Total triglycerides 0.12 (−0.00; 0.24) 0.055 −0.10 (−0.22; 0.02) 0.090 −0.05 (−0.17; 0.07) 0.446 Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 VLDL TG 0.07 (−0.06; 0.19) 0.300 −0.07 (−0.19; 0.06) 0.308 −0.06 (−0.18; 0.07) 0.390 IDL TG 0.18 (0.08; 0.27) <0.001 * −0.16 (−0.25; −0.06) 0.001 * −0.16 (−0.26; −0.07) <0.001 * LDL TG 0.15 (0.06; 0.25) 0.001 * −0.14 (−0.23; −0.04) 0.005 −0.15 (−0.24; −0.05) 0.002 * HDL TG 0.03 (−0.07; 0.12) 0.573 −0.05 (−0.15; 0.05) 0.339 0.00 (−0.09; 0.10) 0.953 Cholesterol Total cholesterol 0.07 (−0.04; 0.17) 0.207 −0.06 (−0.17; 0.05) 0.269 −0.06 (−0.17; 0.04) 0.230 VLDL-C 0.08 (−0.03; 0.19) 0.137 −0.09 (−0.19; 0.02) 0.120 −0.06 (−0.16; 0.05) 0.275 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolites 2022,12, 700 4 of 13 Table 2. Cont. Sedentary Time Light Intensity Physical Activity Moderate-toVigorous Physical Activity Metabolome Measure β(95% CI) p-Value β(95% CI) p-Value β(95% CI) p-Value Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Quantile regression models applied. * statistically significant, p≤0.002. Table 3. Compositional analysis with standardized regression coefficients ( β ) of sedentary time and physical activity intensities for age, education, smoking, alcohol, nutrition-adjusted regression models for serum metabolome. Bonferroni-corrected p-value of ≤ 0.002 was set as the level for statistical significance, which corresponds to a p-value of less than 0.05. Sedentary Time Light Intensity Physical Activity Moderate-toVigorous Physical Activity Metabolome Measure γp-Value γp-Value γp-Value Lipoprotein particle concentration Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Extremely large VLDL 0.091 0.458 −0.284 0.157 0.194 0.289 Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Very large VLDL 0.130 0.354 −0.351 0.127 0.221 0.290 Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Large VLDL 0.111 0.440 −0.235 0.316 0.124 0.559 Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Medium VLDL 0.177 0.251 −0.141 0.576 −0.036 0.875 Small VLDL 0.221 0.082 −0.265 0.201 0.044 0.817 Very small VLDL 0.305 0.018 −0.142 0.499 −0.163 0.395 IDL 0.270 0.041 −0.010 0.961 −0.259 0.186 Large LDL 0.252 0.059 0.002 0.994 −0.253 0.200 Medium LDL 0.248 0.063 −0.010 0.965 −0.238 0.229 Small LDL 0.237 0.076 −0.049 0.823 −0.188 0.342 Very large HDL −0.164 0.228 −0.135 0.541 0.299 0.138 Large HDL −0.332 0.018 −0.116 0.610 0.448 0.031 Medium HDL −0.249 0.079 −0.187 0.419 0.436 0.039 Small HDL 0.076 0.594 −0.174 0.456 0.098 0.643 Metabolites 2022,12, 700 5 of 13 Table 3. Cont. Sedentary Time Light Intensity Physical Activity Moderate-toVigorous Physical Activity Metabolome Measure γp-Value γp-Value γp-Value Lipoprotein particle size VLDL diameter 0.114 0.431 −0.238 0.314 0.124 0.563 LDL diameter −0.037 0.794 0.344 0.136 −0.307 0.143 HDL diameter −0.300 0.031 −0.075 0.743 0.374 0.071 Apolipoproteins ApoA1 −0.243 0.088 −0.237 0.310 0.480 0.024 ApoB 0.265 0.048 −0.141 0.519 −0.124 0.533 ApoB ApoA1 ratio 0.358 0.008 −0.059 0.787 −0.299 0.134 Triglycerides Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Total triglycerides 0.245 0.105 −0.430 0.083 0.185 0.411 Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 VLDL TG 0.133 0.383 −0.248 0.320 0.115 0.612 IDL TG 0.444 <0.001 * −0.203 0.293 −0.240 0.173 LDL TG 0.386 0.001 * −0.166 0.391 −0.219 0.215 HDL TG 0.088 0.474 −0.284 0.156 0.196 0.283 Cholesterol Total cholesterol 0.164 0.222 −0.086 0.695 −0.078 0.697 VLDL-C 0.219 0.104 −0.218 0.323 −0.001 0.997 IDL-C 0.244 0.068 0.018 0.933 −0.262 0.187 LDL-C 0.235 0.080 0.020 0.927 −0.255 0.202 HDL-C −0.289 0.042 −0.134 0.564 0.424 0.046 HDL2-C −0.309 0.029 −0.111 0.630 0.420 0.046 HDL3-C 0.045 0.746 −0.284 0.211 0.239 0.246 Esterified cholesterol 0.160 0.235 −0.085 0.221 −0.075 0.201 Free cholesterol 0.172 0.196 −0.088 0.688 −0.084 0.670 Fatty acids Total fatty acids 0.179 0.183 −0.282 0.200 0.103 0.606 Unsaturation degree −0.295 0.033 0.269 0.235 0.026 0.898 Omega-3 FA 0.040 0.764 −0.114 0.602 0.074 0.710 Omega-3 FA ratio −0.178 0.198 0.119 0.598 0.059 0.776 Docosahexaenoic acid 0.106 0.423 −0.199 0.359 0.093 0.638 Polyunsaturated FA 0.124 0.354 −0.201 0.358 0.077 0.697 Omega-6 FA 0.137 0.308 −0.213 0.332 0.076 0.702 Omega-6 FA ratio −0.212 0.131 0.286 0.214 −0.074 0.725 Linoleic acid 0.125 0.355 −0.236 0.287 0.111 0.581 Saturated FA 0.221 0.101 −0.292 0.187 0.070 0.725 Saturated FA ratio 0.352 0.016 −0.092 0.702 −0.261 0.231 Monounsaturated FA 0.170 0.210 −0.319 0.152 0.149 0.462 Metabolic substrates Glucose −0.241 0.060 0.409 0.051 −0.168 0.377 Glycerol 0.299 0.030 0.083 0.712 −0.382 0.061 Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Acetoacetate 0.443 0.001 * −0.175 0.437 −0.268 0.192 Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 3-hydroxybuturate 0.319 0.002 * −0.029 0.863 −0.290 0.055 Acetate −0.048 0.737 0.043 0.854 0.005 0.982 Citrate 0.047 0.748 −0.101 0.672 0.054 0.802 Lactate 0.208 0.109 −0.457 0.032 0.248 0.200 Pyruvate −0.080 0.536 0.264 0.212 −0.184 0.338 Metabolites 2022,12, 700 6 of 13 Table 3. Cont. Sedentary Time Light Intensity Physical Activity Moderate-toVigorous Physical Activity Metabolome Measure γp-Value γp-Value γp-Value Amino acids Isoleucine (BCAA) 0.262 0.073 −0.274 0.252 0.011 0.959 Leucine (BCAA) 0.339 0.019 −0.354 0.135 0.015 0.946 Valine 0.396 0.005 −0.361 0.117 −0.035 0.867 Alanine 0.061 0.669 −0.227 0.334 0.166 0.437 Glutamine −0.059 0.649 0.149 0.485 −0.090 0.644 Glycine −0.159 0.253 0.250 0.271 −0.091 0.659 Histidine 0.101 0.483 −0.412 0.082 0.310 0.148 Phenylalanine 0.109 0.447 −0.126 0.592 0.017 0.938 Tyrosine −0.134 0.359 0.121 0.614 0.013 0.951 Miscellaneous Glycoproteins 0.167 0.222 −0.06 0.942 −0.151 0.460 Creatinine 0.201 0.159 −0.352 0.132 0.151 0.476 Albumin 0.071 0.572 −0.400 0.052 0.329 0.079 Metabolites 2022, 12, x FOR PEER REVIEW 4 of 14 IDL-C 0.10 (−0.01; 0.20) 0.064 −0.08 (−0.19; 0.03) 0.160 −0.11 (−0.21; −0.00) 0.041 LDL-C 0.10 (−0.01; 0.20) 0.074 −0.07 (−0.18; 0.03) 0.179 −0.10 (−0.21; −0.00) 0.047 HDL-C −0.11 (−0.22; 0.01) 0.064 0.08 (−0.04; 0.19) 0.194 0.12 (0.01; 0.23) 0.029 HDL2-C −0.11 (−0.22; −0.00) 0.046 0.08 (−0.03; 0.20) 0.149 0.13 (0.02; 0.24) 0.022 HDL3-C 0.02 (−0.09; 0.13) 0.731 −0.04 (−0.15; 0.07) 0.517 0.01 (−0.10; 0.11) 0.905 Esterified cholesterol 0.07 (−0.04; 0.17) 0.217 −0.06 (−0.17; 0.05) 0.283 −0.06 (−0.17; 0.04) 0.237 Free cholesterol 0.07 (−0.03; 0.17) 0.187 −0.06 (−0.17; 0.04) 0.239 −0.06 (−0.17; 0.04) 0.219 Fatty acids Total fatty acids 0.07 (−0.04; 0.17) 0.207 −0.08 (−0.19; 0.03) 0.142 −0.04 (−0.14; 0.06) 0.462 Unsaturation degree −0.12 (−0.23; −0.01) 0.028 0.12 (0.01; 0.23) 0.031 0.10 (−0.01; 0.20) 0.074 Omega-3 FA 0.01 (−0.09; 0.12) 0.831 −0.02 (−0.13; 0.09) 0.732 0.00 (−0.10; 0.10) 0.999 Omega-3 FA ratio −0.08 (−0.18; 0.03) 0.168 0.07 (−0.04; 0.19) 0.193 0.06 (−0.04; 0.17) 0.233 Docosahexaenoic acid 0.04 (−0.07; 0.14) 0.466 −0.05 (−0.15; 0.06) 0.379 −0.02 (−0.12; 0.08) 0.700 Polyunsaturated FA 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.16; 0.05) 0.311 −0.03 (−0.13; 0.07) 0.580 Omega-6 FA 0.05 (−0.05; 0.16) 0.320 −0.06 (−0.17; 0.05) 0.267 −0.03 (−0.14; 0.07) 0.522 Omega-6 FA ratio −0.09 (−0.20; 0.02) 0.126 0.10 (−0.02; 0.21) 0.093 0.06 (−0.05; 0.16) 0.307 Linoleic acid 0.05 (−0.06; 0.15) 0.372 −0.06 (−0.17; 0.05) 0.290 −0.03 (−0.13; 0.08) 0.620 Saturated FA 0.08 (−0.02; 0.19) 0.124 −0.09 (−0.20; 0.01) 0.088 −0.05 (−0.16; 0.05) 0.315 Saturated FA ratio 0.13 (0.02; 0.25) 0.025 −0.12 (−0.24; 0.00) 0.051 −0.12 (−0.24; −0.01) 0.032 Monounsaturated FA 0.06 (−0.04; 0.17) 0.235 −0.08 (−0.19; 0.03) 0.136 −0.03 (−0.13; 0.08) 0.577 Metabolic substrates Glucose −0.09 (−0.19; 0.01) 0.086 0.11 (0.01; 0.21) 0.035 0.04 (−0.06; 0.14) 0.390 Glycerol 0.11 (0.00; 0.22) 0.041 −0.08 (−0.19; 0.03) 0.175 −0.13 (−0.24; −0.03) 0.012 Acetoacetate −0.02 (−0.13; 0.09) 0.724 0.02 (−0.09; 0.14) 0.674 0.01 (−0.10; 0.12) 0.847 ǂ 3-hydroxybuturate 0.13 (0.05; 0.21) 0.002 * −0.11 (−0.20; −0.03) 0.011 −0.13 (−0.21; −0.05) 0.001 * ǂ Acetate 0.16 (0.05; 0.26) 0.003 −0.16 (−0.27; −0.05) 0.003 −0.15 (−0.25; −0.05) 0.003 Citrate 0.00 (−0.11; 0.11) 0.996 −0.02 (−0.14; 0.10) 0.725 0.03 (−0.09; 0.14) 0.658 Lactate 0.08 (−0.03; 0.18) 0.148 −0.10 (−0.20; 0.01) 0.067 −0.03 (−0.13; 0.07) 0.514 Pyruvate 0.04 (−0.06; 0.14) 0.403 0.00 (−0.10; 0.11) 0.957 −0.09 (−0.19; 0.01) 0.070 Amino acids Isoleucine (BCAA) 0.10 (−0.01; 0.22) 0.081 −0.11 (−0.23; 0.01) 0.062 −0.07 (−0.18; 0.04) 0.217 Leucine (BCAA) 0.13 (0.02; 0.24) 0.024 −0.14 (−0.26; −0.02) 0.019 −0.10 (−0.21; 0.02) 0.092 Valine 0.16 (0.05; 0.27) 0.004 −0.16 (−0.27; −0.05) 0.006 −0.13 (−0.24; −0.02) 0.018 Alanine 0.02 (−0.09; 0.14) 0.674 −0.05 (−0.17; 0.06) 0.379 0.01 (−0.10; 0.12) 0.798 Glutamine −0.19 (−0.29; −0.09) <0.001 0.20 (0.10; 0.30) <0.001 * 0.13 (0.04; 0.23) 0.008 Glycine −0.07 (−0.18; 0.04) 0.185 0.08 (−0.03; 0.19) 0.167 0.05 (−0.05; 0.16) 0.330 Histidine 0.03 (−0.09; 0.14) 0.664 −0.06 (−0.17; 0.06) 0.351 0.02 (−0.09; 0.13) 0.767 Phenylalanine 0.04 (−0.07; 0.16) 0.444 −0.05 (−0.17; 0.06) 0.378 −0.03 (−0.14; 0.08) 0.647 Tyrosine −0.06 (−0.17; 0.06) 0.317 0.06 (−0.06; 0.17) 0.357 0.05 (−0.06; 0.16) 0.372 Miscellaneous Glycoproteins 0.07 (−0.04; 0.18) 0.193 −0.05 (−0.16; 0.06) 0.342 −0.08 (−0.19; 0.03) 0.137 Creatinine 0.06 (−0.05; 0.17) 0.290 −0.08 (−0.20; 0.03) 0.165 −0.02 (−0.13; 0.09) 0.681 Albumin 0.02 (−0.08; 0.11) 0.762 −0.05 (−0.15; 0.05) 0.345 0.03 (−0.07; 0.13) 0.560 ǂ Quantile regression models applied. * statistically significant, p ≤ 0.002 Quantile regression models applied. * statistically significant, p≤0.002. Significant statistical differences were observed between individuals with high sedentary time and low MVPA compared to individuals with low sedentary time and high MVPA in saturated fatty acid ratio, and acetoacetate and 3-hydroxybuturate concentrations (p≤0.001) (Table 4). In addition, there was a trend (p< 0.05) towards individuals with high sedentary time and low MVPA to exhibit higher concentrations of very small VLDL, IDL, large LDL, medium LDL and small LDL among lipoprotein particles, as well as higher apolipoprotein B and ApoB ApoA1 ratio compared to individuals with low sedentary time and high MVPA. Among triglycerides, the high sedentary time and low MVPA group exhibited a trend for higher triglyceride concentration in IDL and in LDL concentration, and among cholesterols, higher concentrations of IDL and LDL cholesterols compared to their counterparts (p< 0.05). Moreover, a trend for higher concentrations of saturated fatty acid ratio, glycerol, acetoacetate, 3-hydroxybuturate, and lower concentration of glutamine was observed in those with high sedentary time and low MVPA compared to their counterparts (p< 0.05). Table 4. Comparison (mean with standard deviation (SD) and median with interquartile range (IQR)) between a group with high sedentary time and low moderate-to-vigorous physical activity (MVPA) (n= 77), and a group with low sedentary time and high MVPA (n= 86). High Sedentary Time and Low MVPA Low Sedentary Time and High MVPA Metabolome Measure Mean (SD) Median (IQR) Mean (SD) Median (IQR) p-Value Lipoprotein particle concentration Extremely large VLDL 1.0 ×10−10 (9.8 ×10−11) 7.7 ×10−11 (8.6 ×10−11) 8.6 ×10−11 (1.1 ×10−10) 6.1 ×10−11 (1.1 ×10−10) 0.097 1 Very large VLDL 4.7 ×10−10 (5.8 ×10−10) 2.7 ×10−10 (6.3 ×10−10) 4.2 ×10−10 (6.1 ×10−10) 2.1 ×10−10 (5.8 ×10−10) 0.332 1 Large VLDL 3.6 ×10−09 (3.3 ×10−09) 2.4 ×10−09 (3.3 ×10−09) 3.2 ×10−09 (3.5 ×10−09) 2.3 ×10−09 (3.0 ×10−09) 0.259 1 Medium VLDL 1.5 ×10−08 (8.4 ×10−09) 1.1 ×10−08 (9.0 ×10−09) 1.3 ×10−08 (8.8 ×10−09) 1.1 ×10−08 (7.8 ×10−09) 0.251 1 Small VLDL 2.6 ×10−08 (9.8 ×10−09) 2.4 ×10−08 (1.3 ×10−08) 2.4 ×10−08 (9.9 ×10−09) 2.2 ×10−08 (5.4 ×10−08) 0.174 1 Very small VLDL 3.6 ×10−08 (8.5 ×10−09) 3.5 ×10−08 (1.3 ×10−08) 3.3 ×10−08 (7.7 ×10−09) 3.3 ×10−08 (9.6 ×10−09) 0.017 2 IDL 9.9 ×10−08 (2.4 ×10−08) 9.5 ×10−08 (3.7 ×10−08) 8.9 ×10−08 (2.1 ×10−08) 8.9 ×10−08 (2.6 ×10−08) 0.009 2 Large LDL 1.6 ×10−07 (4.3 ×10−08) 1.6 ×10−07 (6.2 ×10−08) 1.5 ×10−07 (3.7 ×10−08) 1.4 ×10−07 (5.0 ×10−08) 0.013 2 Medium LDL 1.3 ×10−07 (3.7 ×10−08) 1.3 ×10−07 (5.1 ×10−08) 1.2 ×10−07 (3.2 ×10−08) 1.2 ×10−07 (4.3 ×10−08) 0.017 2 Small LDL 1.5 ×10−07 (4.1 ×10−08) 1.5 ×10−07 (5.6 ×10−08) 1.4 ×10−07 (3.6 ×10−08) 1.4 ×10−07 (4.7 ×10−08) 0.023 2 Very large HDL 3.7 ×10−07 (1.4 ×10−07) 3.5 ×10−07 (2.0 ×10−07) 3.9 ×10−07 (1.4 ×10−07) 3.8 ×10−07 (2.1 ×10−07) 0.331 2 Large HDL 7.5 ×10−07 (3.4 ×10−07) 7.5 ×10−07 (5.2 ×10−07) 8.6 ×10−07 (3.6 ×10−07) 8.3 ×10−07 (5.7 ×10−07) 0.051 2 Medium HDL 1.6 ×10−06 (2.4 ×10−07) 1.5 ×10−06 (3.5 ×10−07) 1.6 ×10−06 (2.4 ×10−07) 1.6 ×10−06 (2.9 ×10−07) 0.316 2 Small HDL 4.6 ×10−06 (4.0 ×10−07) 4.6 ×10−06 (6.3 ×10−07) 4.5 ×10−06 (3.5 ×10−07) 4.5 ×10−06 (4.4 ×10−07) 0.348 2 Metabolites 2022,12, 700 7 of 13 Table 4. Cont. High Sedentary Time and Low MVPA Low Sedentary Time and High MVPA Metabolome Measure Mean (SD) Median (IQR) Mean (SD) Median (IQR) p-Value Lipoprotein particle size VLDL diameter 36.4 (1.2) 36.2 (1.4) 36.3 (1.3) 36.2 (1.7) 0.639 2 LDL diameter 23.6 (0.1) 23.6 (0.1) 23.6 (0.1) 23.6 (0.1) 0.912 2 HDL diameter 9.8 (0.2) 9.8 (0.4) 9.8 (0.2) 9.8 (0.3) 0.121 2 Apolipoproteins ApoA1 1.31 (0.12) 1.27 (0.15) 1.33 (0.13) 1.34 (0.17) 0.343 2 ApoB 0.82 (0.19) 0.80 (0.25) 0.76 (0.17) 0.75 (0.23) 0.031 2 ApoB ApoA1 ratio 0.63 (0.15) 0.60 (0.19) 0.57 (0.13) 0.56 (0.16) 0.015 2 Triglycerides Total triglycerides 1.07 (0.48) 0.92 (0.53) 0.99 (0.51) 0.87 (0.44) 0.158 1 VLDL TG 0.73 (0.42) 0.57 (0.45) 0.67 (0.44) 0.57 (0.38) 0.232 1 IDL TG 0.092 (0.022) 0.090 (0.033) 0.084 (0.023) 0.080 (0.022) 0.007 1 LDL TG 0.14 (0.037) 0.13 (0.053) 0.12 (0.037) 0.12 (0.040) 0.010 1 HDL TG 0.12 (0.029) 0.11 (0.037) 0.11 (0.031) 0.10 (0.032) 0.259 1 Cholesterol Total cholesterol 3.92 (0.79) 3.85 (1.14) 3.69 (0.73) 3.65 (0.90) 0.058 2 VLDL-C 0.61 (0.23) 0.58 (0.29) 0.56 (0.23) 0.52 (0.27) 0.075 1 IDL-C 0.64 (0.17) 0.62 (0.24) 0.58 (0.14) 0.57 (0.18) 0.012 2 LDL-C 1.51 (0.45) 1.46 (0.63) 1.35 (0.39) 1.34 (0.53) 0.018 2 HDL-C 1.16 (0.22) 1.13 (0.27) 1.21 (0.24) 1.20 (0.35) 0.154 2 HDL2-C 0.67 (0.21) 0.66 (0.26) 0.72 (0.22) 0.71 (0.32) 0.117 2 HDL3-C 0.49 (0.02) 0.49 (0.03) 0.49 (0.02) 0.49 (0.03) 0.543 2 Esterified cholesterol 2.80 (0.57) 2.76 (0.81) 2.64 (0.52) 2.60 (0.63) 0.060 2 Free cholesterol 1.12 (0.22) 1.11 (0.33) 1.06 (0.21) 1.05 (0.25) 0.057 2 Fatty acids Total fatty acids 9.41 (1.93) 9.26 (2.62) 8.95 (1.95) 8.75 (2.40) 0.137 2 Unsaturation degree 1.22 (0.05) 1.23 (0.06) 1.24 (0.05) 1.23 (0.05) 0.060 2 Omega-3 FA 0.36 (0.10) 0.34 (0.13) 0.34 (0.10) 0.33 (0.12) 0.442 2 Omega-3 FA ratio 3.76 (0.57) 3.65 (0.76) 3.81 (0.59) 3.73 (0.80) 0.534 2 Docosahexaenoic acid 0.096 (0.033) 0.091 (0.043) 0.090 (0.033) 0.085 (0.038) 0.277 2 Polyunsaturated FA 3.72 (0.64) 3.71 (0.84) 3.59 (0.61) 3.53 (0.74) 0.199 2 Omega-6 FA 3.36 (0.55) 3.34 (0.74) 3.25 (0.52) 3.18 (0.69) 0.176 2 Omega-6 FA ratio 36.1 (2.6) 36.5 (3.4) 36.7 (2.7) 37.3 (3.2) 0.138 2 Linoleic acid 2.89 (0.47) 2.89 (0.7) 2.81 (0.44) 2.76 (0.59) 0.266 2 Saturated FA 3.23 (0.68) 3.16 (0.95) 3.02 (0.69) 2.96 (0.85) 0.064 2 Saturated FA ratio 34.27 (1.00) 34.39 (1.24) 33.74 (1.06) 33.85 (1.30) 0.001 2,* Monounsaturated FA 2.47 (0.70) 2.34 (0.90) 2.34 (0.73) 2.25 (0.86) 0.132 1 Metabolic substrates Glucose 4.00 (0.38) 3.96 (0.49) 4.04 (0.36) 4.04 (0.42) 0.356 1 Glycerol 0.072 (0.023) 0.066 (0.027) 0.063 (0.019) 0.061 (0.022) 0.008 1 Acetoacetate 0.119 (0.080) 0.095 (0.100) 0.081 (0.053) 0.059 (0.048) <0.001 1,* 3-hydroxybuturate 0.21 (0.13) 0.17 (0.15) 0.16 (0.10) 0.13 (0.07) <0.001 1,* Acetate 0.044 (0.009) 0.043 (0.014) 0.043 (0.010) 0.042 (0.013) 0.532 2 Citrate 0.107 (0.011) 0.107 (0.016) 0.107 (0.012) 0.105 (0.017) 0.749 2 Lactate 0.92 (0.24) 0.89 (0.31) 0.89 (0.23) 0.81 (0.32) 0.263 1 Pyruvate 0.079 (0.017) 0.077 (0.018) 0.075 (0.013) 0.075 (0.018) 0.150 2 Amino acids Isoleucine (BCAA) 0.058 (0.012) 0.057 (0.015) 0.056 (0.015) 0.054 (0.017) 0.096 1 Leucine (BCAA) 0.085 (0.013) 0.084 (0.017) 0.081 (0.015) 0.079 (0.019) 0.139 2 Valine 0.184 (0.023) 0.184 (0.039) 0.178 (0.027) 0.181 (0.034) 0.132 2 Alanine 0.365 (0.052) 0.361 (0.070) 0.359 (0.042) 0.347 (0.058) 0.445 2 Glutamine 0.502 (0.059) 0.498 (0.078) 0.537 (0.085) 0.529 (0.103) 0.005 1 Glycine 0.229 (0.027) 0.224 (0.032) 0.233 (0.027) 0.232 (0.034) 0.282 1 Histidine 0.069 (0.006) 0.069 (0.009) 0.069 (0.007) 0.069 (0.009) 0.737 1 Phenylalanine 0.068 (0.009) 0.066 (0.010) 0.068 (0.007) 0.067 (0.007) 0.741 2 Tyrosine 0.051 (0.009) 0.05 (0.013) 0.052 (0.009) 0.053 (0.011) 0.496 2 Miscellaneous Glycoproteins 1.25 (0.18) 1.21 (0.23) 1.23 (0.17) 1.20 (0.17) 0.566 1 Creatinine 0.071 (0.009) 0.070 (0.012) 0.069 (0.008) 0.069 (0.011) 0.159 2 Albumin 0.089 (0.005) 0.089 (0.007) 0.089 (0.005) 0.089 (0.007) 0.572 2 1Mann–Whitney test, 2independent-samples t-test. * statistically significant, p≤0.002. 3. Discussion Among young healthy adult men, there were statistically significant and a trend towards significant associations of accelerometer-based sedentary time and physical activity with selected serum metabolome measures. Compositional analysis revealed that 4 metabolome variables were significantly associated with sedentary time and altogether 15 variables with a trend towards significant associations with varying metabolic pathways Metabolites 2022,12, 700 8 of 13 with sedentary time (13 variables) and moderate-to-vigorous physical activity (5 variables). The present study revealed possible mechanistic pathways relevant for the interaction between sedentary behavior, physical activity and ketone bodies as well as amino acid concentration both related to exercised-induced energy production and lipid metabolism. Moreover, selected lipoprotein, cholesterol, and fatty acid concentrations were trending towards significant associations with sedentary time and physical activity in young healthy adult men emphasizing the role of HDL metabolism. Interestingly, one of the most consistent findings of the present study was that ketone bodies, acetoacetate and 3-hydroxybutrate were associated across all exposure variables, sedentary time and physical activity, in the linear regression analysis. We have previously observed similar associations in the same study sample [ 14 ], where both aerobic and maximal strength were associated with acetoacetate and 3-hydroxybutrate. Although only sedentary time was significantly associated with ketone bodies in the compositional analysis, these results may suggest that sedentary time, physical activity, and physical fitness may all be mechanistically related to fat catabolism. Interestingly, these associations remained even after adjustments for body fat or aerobic fitness for 3-hydroxybutrate and partly for acetoacetate. Previously, it has been postulated that BCAA degradation is linked with tricarboxylic acid cycle, intramyocellular lipid storage and oxidation enabling efficiency in lipid metabolism [ 15 ]. We also observed a trend towards significant associations in single regression models of sedentary time and physical activity with selected branch chain amino acids (BCAA), namely valine and leucine, but also with glutamine. Although only sedentary time was significantly associated with valine and leucine in the compositional analysis, the few previous study results support these findings [6,7]. These results may indicate that both reduced sedentary time and increased physical activity may have beneficial health-related associations with BCAA via their mechanistic pathways in physical-activity-induced energy production. In regards of this, the present study results emphasize the role of sedentary time. Possible mechanistic pathways may include the triggering effect of physical activity on BCAA oxidation in skeletal muscles and activation of enzymes related to protein degradation [16]. Previous studies with self-reported physical activity have shown associations with the metabolome in adults [ 6 , 8 , 9 ]; however, there are only a few accelerometer-based physical activity studies. These studies have shown selected associations between physical activity and metabolome. Bell et al. (2018) reported in children that total physical activity measured with accelerometer was significantly associated with fatty acid profile, namely cholesterol and triglycerides in HDL and VLDL particles, and glycoproteins acetyls with the strongest associations evident for higher intensity physical activity [ 10 ]. Although all associations were weak in magnitude, they were stronger for physical activity than for sedentary time. Another study on children [ 13 ] showed that accelerometer-based moderate-to-vigorous physical activity and sedentary time were associated with lipoprotein particle profile at the follow-up year after. In adults, accelerometer-based measurements of physical activity were inversely associated with selected amino acids and glucose metabolism among the metabolome profile [ 7 ]. Bell et al. (2018) reported in children that associations between metabolomics and MVPA tended to be greater than that of sedentary time [ 10 ]. In line with the present study, a recent meta-analysis [ 17 ] observed limited evidence for the association between light intensity physical activity and conventional cardiometabolic risk factors. In the present study, we found none of such associations in the compositional analysis, except a trend towards an inverse association between light intensity physical activity and lactate concentration, whereas moderate-to-vigorous physical activity was trending towards significant associations with five metabolome outcomes, all related to HDL metabolism. Among the metabolome variables related to lipid metabolism with a trend towards significant associations with both sedentary time and moderate-to-vigorous physical activity, there were altogether seven variables directly related to HDL metabolism. This is in line with several previous studies, where an association between physical activity