Changes in Lipoinflammation Markers in People with Obesity after a Concurrent Training Program: A Comparison between Men and Women

In e na ional Jou nal o En i onmen al Resea ch and Public Heal h A icle Changes in Lipoin lamma ion Ma ke s in People wi h Obesi y a e a Concu en T aining P og am: A Compa ison be ween Men and Women JoséAn onio González-Ju ado 1, Wal e Suá ez-Ca mona 2, Se gio López 3,4 and An onio Jesús Sánchez-Oli e 5,* 1Facul ad de Ciencias del Depo e; Uni e sidad Pablo de Ola ide de Se illa, 41013 Se illa, Spain; [email p o ec ed] 2In es igado Sis ema de In o mación Cien í ica de Andalucía, Uni e sidad Pablo Ola ide de Se illa, 41013 Se illa, Spain; [email p o ec ed] 3 Labo a o y o Cellula and Molecula Nu i ion, Ins . de la G asa, CSIC, 41013 Se ille, Spain; [email p o ec ed] 4Depa men o Cell Biology, Uni e si y o Se ille, 41012 Se ille, Spain 5Depa amen o de Mo icidad Humana y Rendimien o Depo i o, Uni e sidad de Se illa, 41013 Se illa, Spain *Co espondence: [email p o ec ed] Recei ed: 31 July 2020; Accep ed: 24 Augus 2020; Published: 25 Augus 2020   Abs ac : Obesi y is ela ed o low-g ade sys emic in lamma ion. This s a e o in lamma ion is cha ac e ized by he al e a ion in adipokine egula ion, which may lead o a si ua ion o ca diome abolic isk. The aim o his s udy was o e alua e he e ec s o a concu en aining p og am on ma ke s o lipoin lamma ion in adul people wi h obesi y, compa ing he esponse o he aining be ween men and women. A quasi-expe imen al, quan i a i e, and longi udinal s udy wi h a p e–pos in e en ion was conduc ed. An 8-week concu en aining p og am was ca ied ou , in which 26 indi iduals wi h obesi y pa icipa ed (mean ± SD; age =46.38 ± 4.66) (BMI =36.05 ± 4.99) (12 men and 14 women). Be o e and a e he in e en ion pe iod, blood samples we e aken by pe cu aneous punc u e. The blood le els o adiponec in and lep in we e e alua ed. Signi ican di e ences we e ob ained in he adiponec in–lep in a io (A/L a io) o he en i e sample (p=0.009, ES =0.53), which indica es a dec ease in he isk o ca dio ascula diseases and lipoin lamma ion. The e we e no signi ican di e ences in he imp o emen s obse ed a e he aining in A/L a io be ween women (A/L change = +63.5%) and men (A/L change= +59.2%). I can be concluded ha he combina ion o ae obic exe cise and esis ance aining induced an imp o emen in ma ke s o lipoin lamma ion and ca diome abolic isk in he indi iduals wi h obesi y e alua ed in his s udy. Keywo ds: o e weigh ; seden a yli es yle; physicalexe cise; adiponec in; lep in; adiponec in-lep in a io 1. In oduc ion The wo ldwide expansion o obesi y is a eason o conside i a pandemic nowadays. The Wo ld Heal h O ganiza ion (WHO) de ines o e weigh and obesi y as an abno mal o excessi e accumula ion o a ha poses a heal h isk [ 1 ]. Despi e his ela i ely simplis ic de ini ion, obesi y is a ch onic, mul i ac o ial, and mul icausal disease, which co esponds o an al e a ion o he co ec unc ion o he adipose issue in i s capaci y o s o e a , bo h quan i a i ely and quali a i ely [ 2 ]. In addi ion, i leads o an in lamma o y condi ion o he a o emen ioned issue (lipoin lamma ion), closely linked o me abolic diso de s, which in u n a e s ongly associa ed wi h he me abolic synd ome [2]. Al hough an inc ease o he o al body a is associa ed wi h an inc ease o heal h isk, he amoun o abdominal a , pa icula ly when i is ound wi hin he abdominal ca i y, has been associa ed wi h In . J. En i on. Res. Public Heal h 2020,17, 6168; doi:10.3390/ije ph17176168 www.mdpi.com/jou nal/ije ph In . J. En i on. Res. Public Heal h 2020,17, 6168 2 o 12 an inc ease o he isk o como bidi y and mo ali y o di e en easons. Thus, we obse e a highe p e alence o ype 2 diabe es, hea disease, s oke, sleep apnea, hype ension, dyslipidemia, insulin esis ance, in lamma ion, and some ypes o cance [ 2 ]. All hese diseases ha e nega i e e ec s on he quali y o li e, wo k p oduc i i y, and he cos s o medical assis ance [3,4]. Li es yle changes a e a c i ical pa o obesi y p e en ion and in e en ion and a e being pu sued by public heal h o ganiza ions o p omo e heal h [ 5 ]. Physical inac i i y and seden a y beha io a e wo powe ul d i e s o he obesi y pandemic [ 6 ] and ha e been linked o an inc eased p e alence o disease and an inc eased isk o all-cause mo ali y [7]. Obesi y has been ecognized as a sys emic low-g ade in lamma o y s a e, cha ac e ized by an inc ease o in lamma o y ac o s and in il a ion o immune cells, wi h no lesions o al e a ions in issue s uc u e o unc ion [ 2 ]. I has been epo ed ha obesi y is associa ed wi h an a ypical ac i a ion o p oin lamma o y signaling in he hypo halamus [ 8 ]. Al hough he e a e no al e a ions in cell mo phology a he his ological le el, a he plasma ic le el he e is an inc ease o p oin lamma o y cy okines, such as TNF- α , IL-1b, IL-6, and C- eac i e p o ein, as well as in il a ion o mac ophages and T lymphocy es in insulin-dependen issues, among o he s, which igge s ac o s such as oxida i e s ess and insulin esis ance [9]. Adipose issue (AT) is a p imo dial connec i e issue in he ene gy s o age o e e y o ganism, and i mainly consis s o adipocy es. I ca ies ou au oc ine, endoc ine, and pa ac ine unc ions on he es o he o gans, pa icipa ing in he egula ion o ene ge ic homeos asis, glucose and lipid me abolism, and ho mone modula ion, and i also plays a ele an ole in he in lamma o y p ocess [ 10 ]. When a hype ophic adipocy e exceeds i s h eshold capaci y, i s no mal ac i i y s ops, showing a dec ease in insulin sensi i i y, hypoxia, an inc ease in cell s ess, and consequen ly cell apop osis, hus ac i a ing he in lamma o y p ocess [ 11 ]. AT sec e es a se ies o p oin lamma o y and an i-in lamma o y adipokines, o which he mos popula a e lep in and adiponec in. Lep in is a p o ein ha pe o ms i s physiological ac i i y h ough i s ecep o LEP-R (lep in ecep o ). The binding o lep in o i s ecep o in he hypo halamus igge s a se ies o chemical signals ha a ec s he eeling o hunge and help o p oduce he eeling o sa ie y. An excess o lep in in he adipocy e p omo es he in lamma o y e ec and dec eases insulin sensi i i y [ 12 ]. Adiponec in is he mos abundan adipokine in human blood, wi h physiological le els o 5–30 ug/mL. I is sec e ed by he AT, mainly by whi e adipose issue (WAT) [ 13 ]. Adiponec in is a p o ein ho mone ha plays an an i-in lamma o y ole wi hin he adipose issue. P e ious s udies ha e shown insulin-sensi izing, an i-a he ogenic, and an i-in lamma o y e ec s [ 2 ]. This ole o adiponec in in he in lamma o y p ocess is pa icula ly posi i e in pa ien s wi h me abolic diseases such as ype 2 diabe es melli us and obesi y, who ha e shown low-g ade ch onic in lamma ion and low se um adiponec in concen a ions [ 4 ]. The e o e, lep in and adiponec in play an impo an ole in he heal h o he indi idual and his adipose issue. Lep in egula es inna e and adap i e esponses h ough he modula ion o he ac i i y and p oli e a ion o immune cells; hus, i can egula e he pola iza ion owa d a p oin lamma o y pheno ype. On he o he hand, adiponec in shows an i-in lamma o y p ope ies, s imula es lipid oxida ion, and imp o es glucose me abolism by inc easing insulin sensi i i y. Adipocy e hype ophy p oduces an imbalance in hese ho mones, p omo ing he p oduc ion o lep in and educing ha o adiponec in; pa icipa ing in ad e se signals om adipose issue ha can lead o seconda y issue damage ha inc eases concomi an lipo oxici y [ 2 , 14 ]. The e o e, he adiponec in/lep in a io (A/L a io) is iden i ied as a ma ke o adipose issue ailu e. I has been demons a ed ha his index is s ongly associa ed wi h insulin esis ance, showing a s onge ela ionship wi h he isk o de eloping ype 2 diabe es compa ed o he analysis o lep in o adiponec in sepa a ely [15]. The A/L a io is a good indica o o a mal unc ioning adipose issue and i is nega i ely associa ed wi h ma ke s o low-g ade ch onic in lamma ion; hus, i can be a use ul s imula o o he ca diome abolic isk associa ed wi h obesi y [ 16 ]. Al hough he measu emen me hod used mus be aken in o accoun , i is conside ed ha a no mal A/L a io should ha e alues abo e 1.0 (adiponec in le els exp essed in µ g/mL and lep in le els in ng/mL), whe eas an A/L a io be ween 0.5 In . J. En i on. Res. Public Heal h 2020,17, 6168 3 o 12 and 1.0 ep esen s a mode a e/medium ca diome abolic isk, and a p opo ion below 0.5 is a se ious indica o o ca diome abolic isk [17]. Nume ous au ho s ag ee in he e ec s o physical exe cise on he AT [ 18 – 21 ], such as changes in he AT pheno ype ha lead o a signi ican dec ease o M1 mac ophages and an inc ease o M2 mac ophages, as well as he sec e ion o mo e an i-in lamma o y cy okines, such as IL-6 and TNF- α [ 22 ]. O he esea che s ha e s udied he possible changes in he signaling pa hways a e implemen ing exe cise p og ams, epo ing a dec ease o pos p andial lipemia, a educ ion in NF-kB signaling, and an inc ease in AMPK signaling (showing an i-in lamma o y p ope ies) [ 23 – 25 ]. The in e es o hese s udies is inc easingly ocused on de e mining he mos adequa e aining o educe he in lamma o y s a e and i s e ec s on me abolic synd ome in people wi h obesi y. The e is scien i ic e idence ha ae obic aining imp o es he le els o p oin lamma o y cy okines (TNF- α , IL-6, and IL-8) in people wi h obesi y and ype 2 diabe es [ 26 ]. In ac , ae obic o ca dio espi a o y exe cise p og ams a e he mos equen ly implemen ed [ 27 ]. Howe e , o he s udies ha e analyzed he impac o esis ance aining o a combina ion o esis ance and ae obic aining on low-g ade ch onic in lamma ion in people wi h obesi y and o e weigh [ 28 – 31 ]. E en me hodologies o highly specialized aining wi h high-in ensi y in e al aining (HIIT) ha e been implemen ed o compa e hei e ec on he in lamma o y s a e o people wi h obesi y and no mal weigh [32]. The aim o his s udy was o e alua e he e ec s o an 8-week concu en aining p og am on ma ke s o lipoin lamma ion (adiponec in, lep in, and adiponec in-lep in a io) in 26 adul people wi h obesi y, compa ing he esponse o he aining be ween men and women. 2. Ma e ials and Me hods This is a quasi-expe imen al, quan i a i e, and longi udinal s udy wi h a p e–pos in e en ion. A o al o 26 indi iduals pa icipa ed in he s udy (12 men and 14 women), wi h an age ange o 38 o 54 yea s (46.38 ± 4.66) and obesi y (BMI =36.05 ± 4.99). Table 1shows baseline and Figu e 1shows a lowcha o he pa icipan selec ion p ocess ollowed in he s udy. Table 1. Pa icipan s’ baselines. Male Female All Mean ±SD Range Mean ±SD Range Mean ±SD Range Age (y ) 46.42 ±5 38–54 46.36 ±4.53 40–53 46.38 ±4.66 38–54 Heigh (m) 1.75 ±0.07 1.6–1.9 1.61 ±0.08 1.44–1.73 1.67 ±0.10 1.44–1.9 Weigh (kg) 109.9 ±16.35 87–140 94.67 ±21.95 70.7–147 101.73 ±20.7 70.7–147 BMI 35.98 ±3.98 30.1–42.2 36.12 ±5.87 30.05–49.69 36.05 ±4.99 30–49.7 BFM (kg) 43.86 ±11.08 24–58.4 45.11 ±14.70 30.8–79.3 44.53 ±12.92 24–79.3 BFMP (%) 39.53 ±5.94 28–48.8 47.59 ±4.63 39–53.9 43.87 ±6.59 28–53.9 BMI: Body Mass Index. BFM: Body Fa Mass; BFMP: Body Fa Mass Pe cen . In . J. En i on. Res. Public Heal h 2020,17, 6168 4 o 12 In . J. En i on. Res. Public Heal h 2020, 17, x FOR PEER REVIEW 13 o 12 Figu e 1. Rec ui men lowcha . The ollowing inclusion c i e ia we e applied; (i) 35–55 yea s o age; (ii) BMI: > 30; (iii) abdominal pe ime e : > 90 cm in women and> 100 cm in men; (i ) a %: > 40 in women and > 30 in men; ( ) signed in o med consen ; and ( i) o icial medical au ho iza ion ha allowed he pa icipan o ca y ou he p og am o planned exe cises. Simila ly, he ollowing exclusion c i e ia we e applied; (i) diagnosis o a pa hology in ol ing an in lamma o y p ocess (e.g., myoca dial in a c ion in he las 12 mon hs, heuma oid a h i is, ib omyalgia, and a h osis), and (ii) ailing o comple e 75% o he aining sessions. The s udy mee s he equi emen s o he Decla a ion o Helsinki o he Wo ld Medical Associa ion (2013) abou he e hical p inciples o esea ch wi h human beings, and i was app o ed by he E hics Commi ee o he Uni e si y o Pablo de Ola ide (Se ille, Spain). The independen a iable was a concu en aining p og am ca ied ou o 8 weeks, wi h 3 weekly sessions o ~60 min each in al e na e days (Monday, Wednesday, and F iday). The ainings we e conduc ed in he ime ame o 5:30 p.m. o 8:30 p.m. o accommoda e he indi idual needs o each pa icipan (wo k, amily, pe sonal, e c.) (Figu e 2). Each aining session began wi h a gene al join mobili y (5 min) and ca dio ascula ac i a ion (5 min), ollowed by a ca dio espi a o y esis ance exe cise ( h ee possible op ions: eadmill, cycle e gome e , o ellip ical bike). This ask was ca ied ou o 12 min a a medium–low in ensi y. The in ensi y was de e mined using Bo g’s a e o pe cei ed exe ion (RPE), aiming o each a RPE alue o 4–5 ou o 10 [33]. Then, a esis ance aining was conduc ed, wi h a 10-s a ion ci cui . Figu e 2 shows he en exe cises p oposed, which in ol e he main muscle g oups used in he mos habi ual basic mo o skills and global mo o ac ions o daily li ing (walking, unning, h owing, ca ying weigh , e c.). Figu e 1. Rec ui men lowcha . The ollowing inclusion c i e ia we e applied; (i) 35–55 yea s o age; (ii) BMI: >30; (iii) abdominal pe ime e : >90 cm in women and >100 cm in men; (i ) a %: >40 in women and >30 in men; ( ) signed in o med consen ; and ( i) o icial medical au ho iza ion ha allowed he pa icipan o ca y ou he p og am o planned exe cises. Simila ly, he ollowing exclusion c i e ia we e applied; (i) diagnosis o a pa hology in ol ing an in lamma o y p ocess (e.g., myoca dial in a c ion in he las 12 mon hs, heuma oid a h i is, ib omyalgia, and a h osis), and (ii) ailing o comple e 75% o he aining sessions. The s udy mee s he equi emen s o he Decla a ion o Helsinki o he Wo ld Medical Associa ion (2013) abou he e hical p inciples o esea ch wi h human beings, and i was app o ed by he E hics Commi ee o he Uni e si y o Pablo de Ola ide (Se ille, Spain). The independen a iable was a concu en aining p og am ca ied ou o 8 weeks, wi h 3 weekly sessions o ~60 min each in al e na e days (Monday, Wednesday, and F iday). The ainings we e conduc ed in he ime ame o 5:30 p.m. o 8:30 p.m. o accommoda e he indi idual needs o each pa icipan (wo k, amily, pe sonal, e c.) (Figu e 2). Each aining session began wi h a gene al join mobili y (5 min) and ca dio ascula ac i a ion (5 min), ollowed by a ca dio espi a o y esis ance exe cise ( h ee possible op ions: eadmill, cycle e gome e , o ellip ical bike). This ask was ca ied ou o 12 min a a medium–low in ensi y. The in ensi y was de e mined using Bo g’s a e o pe cei ed exe ion (RPE), aiming o each a RPE alue o 4–5 ou o 10 [ 33 ]. Then, a esis ance aining was conduc ed, wi h a 10-s a ion ci cui . Figu e 2 shows he en exe cises p oposed, which in ol e he main muscle g oups used in he mos habi ual basic mo o skills and global mo o ac ions o daily li ing (walking, unning, h owing, ca ying weigh , e c.). In . J. En i on. Res. Public Heal h 2020,17, 6168 5 o 12 6 o 12 In . J. En i on. Res. Public Heal h 2020, 17, x; doi: FOR PEER REVIEW www.mdpi.com/jou nal/ije ph Figu e 2. Summa y o he aining p og am and aining session. The wo king ime in each s a ion was 45 s in he i s wo weeks, and i was inc eased o 60 s om he hi d week. The es ing ime be ween exe cises was 45 s in he i s wo week and 30 s om he second week. In he i s wo weeks, wo ci cui s we e comple ed in each session, wi h a passi e es o 2 min. A e he hi d week, he ci cui was comple ed 3 imes in each session, keeping he es ing ime o 2 min. The in ensi y o he exe ion was measu ed h ough he RPE scale OMNI-RES, aiming o each and main ain alues o 6–7 ou o 10 [34]. E e y session ended wi h cooling exe cises (Figu e 2). The planned aining ( empo aliza ion, o ganiza ion, me hodology, aining load le els, cha ac e is ics o he exe cises, e c.) allowed each pa icipan o unde go an indi idualized aining s imulus. In his s udy, i was ne e in ended o s anda dize a closed and igid aining p og am. In his sense, each pa icipan , depending on hei physical capaci y, unde wen a aining s imulus ha posed a ela i e subjec i e in ensi y simila o ha o he es o he sample. The e o e, simple exe cises we e selec ed, in e ms o execu ion and adap a ion o he indi idual capaci ies. The blood ma ke s analyzed we e lep in and adiponec in. Endo enous punc u e equipmen and ubes we e used o he collec ion o biological samples. Endo enous blood was ex ac ed by pe cu aneous punc u e using app op ia e needles and sy inges. These echniques a e minimally in asi e, p ac ically ha mless, and pose no se ious h ea o he pa icipan s. Fo he s a is ical analyses, he IBM SPSS S a is ics 23 so wa e (SPSS Inc., Chicago, IL, USA) was used. Rega ding he desc ip i e s a is ics, he mean and s anda d de ia ion we e calcula ed. The eliabili y o he measu emen s was es ima ed a a 95% con idence in e al o he mean. Rega ding he in e en ial s a is ics, a pai ed-sample o Wilcoxon es was conduc ed o in ag oup compa isons, depending on he no mali y (assessed h ough he Shapi o–Wilk es ), and an independen -samples o Mann–Whi ney U es , depending on he no mali y and he Le ene es . Cohen’s d e ec size was also calcula ed [35], conside ing alues o d < 0.3 as small, d = 0.3–0.5 as mode a e, d = 0.5–0.7 as la ge, d = 0.7–0.9 as e y la ge, and d > 0.9 as ex emely la ge [36]. 3. Resul s Table 2 shows he p e–pos compa ison o he en i e sample. As can be seen, he e was a signi ican inc ease in he adiponec in/lep in a io a he end o he in e en ion pe iod wi h espec Figu e 2. Summa y o he aining p og am and aining session. The wo king ime in each s a ion was 45 s in he i s wo weeks, and i was inc eased o 60 s om he hi d week. The es ing ime be ween exe cises was 45 s in he i s wo week and 30 s om he second week. In he i s wo weeks, wo ci cui s we e comple ed in each session, wi h a passi e es o 2 min. A e he hi d week, he ci cui was comple ed 3 imes in each session, keeping he es ing ime o 2 min. The in ensi y o he exe ion was measu ed h ough he RPE scale OMNI-RES, aiming o each and main ain alues o 6–7 ou o 10 [ 34 ]. E e y session ended wi h cooling exe cises (Figu e 2). The planned aining ( empo aliza ion, o ganiza ion, me hodology, aining load le els, cha ac e is ics o he exe cises, e c.) allowed each pa icipan o unde go an indi idualized aining s imulus. In his s udy, i was ne e in ended o s anda dize a closed and igid aining p og am. In his sense, each pa icipan , depending on hei physical capaci y, unde wen a aining s imulus ha posed a ela i e subjec i e in ensi y simila o ha o he es o he sample. The e o e, simple exe cises we e selec ed, in e ms o execu ion and adap a ion o he indi idual capaci ies. The blood ma ke s analyzed we e lep in and adiponec in. Endo enous punc u e equipmen and ubes we e used o he collec ion o biological samples. Endo enous blood was ex ac ed by pe cu aneous punc u e using app op ia e needles and sy inges. These echniques a e minimally in asi e, p ac ically ha mless, and pose no se ious h ea o he pa icipan s. Fo he s a is ical analyses, he IBM SPSS S a is ics 23 so wa e (SPSS Inc., Chicago, IL, USA) was used. Rega ding he desc ip i e s a is ics, he mean and s anda d de ia ion we e calcula ed. The eliabili y o he measu emen s was es ima ed a a 95% con idence in e al o he mean. Rega ding he in e en ial s a is ics, a pai ed-sample o Wilcoxon es was conduc ed o in ag oup compa isons, depending on he no mali y (assessed h ough he Shapi o–Wilk es ), and an independen -samples o Mann–Whi ney U es , depending on he no mali y and he Le ene es . Cohen’s d e ec size was also calcula ed [ 35 ], conside ing alues o d <0.3 as small, d =0.3–0.5 as mode a e, d =0.5–0.7 as la ge, d=0.7–0.9 as e y la ge, and d >0.9 as ex emely la ge [36]. 3. Resul s Table 2shows he p e–pos compa ison o he en i e sample. As can be seen, he e was a signi ican inc ease in he adiponec in/lep in a io a he end o he in e en ion pe iod wi h espec o he baseline si ua ion, wi h a mode a e e ec size. The e we e no signi ican di e ences in he esul s ob ained in he a iables “adiponec in” and “lep in”. In . J. En i on. Res. Public Heal h 2020,17, 6168 6 o 12 Table 2. In ag oup compa isons. Whole sample (n =26). P e-Tes Pos -Tes Change p§ Value E.S ¥ Mean ±SD CI (95%) Mean ±SD CI (95%) Mean ±SD CI (95%) Adiponec i (ug/mL) 16.94 ±4.89 (14.9–18.6) 17.3 ±5.1 (15.2–19.3) 0.32 ±3.04 ( − 0.91–1.55) 0.20 0.06 Lep in (ng/mL) 44.09 ±24.3 (34.3–53.9) 41.6 ±30.5 (29.3–53.9) −2.5 ±20.1 ( − 10.6–5.59) 0.47 −0.09 A/L a io * 0.5 ±0.32 (0.37–0.63) 0.82 ±0.79 (0.5–1.14) 0.32 ±0.57 (0.09–0.55) 0.009 * 0.53 § S uden - es o Wilcoxon depending on he no mali y; ¥ Cohen’s e ec size (d <0.3 small; d =0.3–0.5 mode a e; d=0.5–0.7 la ge; d =0.7–0.9 e y la ge and d >0.9 ex emely la ge). * Adiponec in/lep in a io. Table 3shows he esul s ob ained when compa ing he a iables “adiponec in” and “lep in” be o e and a e he in e en ion in he women’s g oup. The e we e no signi ican di e ences in he le els o adipokines. Howe e , he A/L a io did show a s a is ically signi ican imp o emen (p=0.05) wi h a la ge e ec size (d =0.55). Table 3. In ag oup compa isons. Women (N =14). P e-Tes Pos -Tes Change p§ Value E.S ¥ CI (95%) Mean ±SD CI (95%) Mean ±SD CI (95%) Mean ±SD Mean ±SD Adiponec in (ug/mL) 18.24 ±3.8 (16.04–20.43) 18.17 ±1.16 (15.67–20.67) −0.06 ±3.63 (−2.16–2.03) 0.55 −0.02 Lep in (ng/mL) 46.5 ±23.8 (32.7–60.2) 46.1 ±37.6 (2.44–6.78) −0.4 ±21.52 (−12.8–12.0) 0.82 −0.01 A/L a io * 0.51 ±0.28 (0.35–0.67) 0.85 ±0.8 (0.39–1.31) 0.34 ±0.62 (−0.01–0.7) 0.05* 0.55 § S uden - es o Wilcoxon depending on he no mali y. ¥ Cohen’s e ec size (d <0.3 small; d =0.3–0.5 mode a e; d=0.5–0.7 la ge; d =0.7–0.9 e y la ge and d >0.9 ex emely la ge). * Adiponec in/lep in a io. Table 4shows he alues ob ained in he men’s g oup, which we e simila o hose obse ed in he women’s g oup, i.e., he e we e no signi ican di e ences in he le els o adipokines be ween he p e- es and he pos - es . In his case, al hough he A/L a io imp o ed, his inc ease was no s a is ically signi ican (p=0.08); howe e , he e ec size o his inc ease can be conside ed as mode a e (d =0.46). Table 4. In ag oup compa isons. Men (N =12). P e-Tes Pos -Tes Change p Value §E.S ¥ Mean ±SD CI (95%) Mean ±SD CI (95%) Mean ±SD CI (95%) Adiponec in (ug/mL) 15.43 ±5.71 (11.8–19.1) 16.2 ±5.71 (12.57–19.83) 0.76 ±2.25 (−0.67–2.2) 0.26 0.12 Lep in (ng/mL) 41.32 ±25.6 (25.1–57.6) 36.36 ±19.86 (23.7–48.9) − 4.96 ± 18.82 (−16.9–6.9) 0.38 −0.22 A/L a io * 0.49 ±0.37 (0.25–0.73) 0.78 ±0.81 (0.27–1.29) 0.29 ±0.53 (−0.05–0.63) 0.08 0.46 § S uden - es o Wilcoxon acco ding o no mali y. ¥ Cohen’s e ec size (d <0.3 small; d =0.3–0.5 mode a e; d=0.5–0.7 la ge; d =0.7–0.9 e y la ge and d >0.9 ex emely la ge). * Adiponec in/Lep in a io. The esul s o he in e g oup compa isons (women s. men) a e ep esen ed in Figu e 3. The p e–pos di e ences a e compa ed, exp essed in pe cen ages. As can be obse ed, he di e ences be ween men and women a e e y small; in ac , he e we e no s a is ically signi ican di e ences in any o he h ee a iables. I is wo h highligh ing ha he A/L a io inc eased conside ably in he wo g oups and in a simila manne , sugges ing ha bo h imp o ed his index o he same ex en . In . J. En i on. Res. Public Heal h 2020,17, 6168 7 o 12 In . J. En i on. Res. Public Heal h 2020, 17, x FOR PEER REVIEW 13 o 12 Figu e 3. Changes a e in e en ion compa isons. No signi ican di e ences we e ound be ween sex g oups. S uden - es o Mann–Whi ney U we e ca ied ou depending on he no mali y and Le ene es . 4. Discussion The aim o his s udy was o analyze he e ec s o a physical exe cise p og am based on concu en aining on lipoin lamma ion ma ke adipokines in adul s wi h obesi y, compa ing he esponses be ween men and women. Table 2 compa es he esul s o he en i e sample (n = 26), showing ha he ini ial a e age lep in le els we e 44.09 ng/mL. These le els a e associa ed wi h g ea e insulin esis ance, and hey a e usually ound in people wi h a BMI abo e 30. The esul s show an imp o emen o hese alues a e he in e en ion, om 44.09 down o 41.59 ng/mL, al hough his dec ease was small (−2.5 ng/mL) and no s a is ically signi ican . The changes in adiponec in we e also posi i e, ha is, he e was an inc ease in i s blood le els (+0.32 ug/mL), al hough his inc ease was no s a is ically signi ican ei he . The esul s a e p esen ed sepa a ely by sex in Tables 3 and 4. These esul s a e simila o hose ob ained conside ing he en i e sample. The e we e signs o imp o emen in adiponec in and lep in, al hough such changes we e e y small. On he o he hand, he e we e mo e conside able di e ences in he inc eases in he A/L a io, which we e signi ican in he women’s g oup (p = 0.5) and close o s a is ical signi icance in he men’s g oup (p = 0.08), wi h a la ge e ec size in women (0.55) and mode a e in men (0.46). In nume ous s udies, people wi h obesi y ha e conduc ed di e en aining p og ams, epo ing imp o emen s in he plasma ic le els o lep in [37–40], wi h signi ican dec eases. Likewise, a la ge numbe o s udies ha e analyzed he e ec s o di e en physical exe cise p og ams on he concen a ions o adiponec in [41–44]. In he p esen s udy, he changes in adiponec in and lep in we e lowe , p obably due o he ac ha he in e en ion pe iod was conside ably sho e compa ed o ha o he ci ed s udies [37,42,45], o because hei in e en ions e alua ed he acu e e ec o exe cise p og ams o highe in ensi y [43,44]. O he s udies combined he aining wi h he adminis a ion o e gogenic o an i- in lamma o y supplemen s [41]. The imp o emen s in he le els o adiponec in and lep in, analyzed independen ly, we e no signi ican ; howe e , he A/L a io did ob ain a signi ican inc ease a e he aining pe iod (p = 0.009), wi h a la ge e ec size (0.53).The A/L a io is a bioma ke ha has been well s udied in i s ela ionship -0.38% -0.86% 63% 5% -12% 59% 1.89% -5.67% 64% -15% 0% 15% 30% 45% 60% 75% Adiponec in Lep in A/L Ra io Change Pe cen Female s. Male compa isons di e ences pos es —p e es Female Male All Figu e 3. Changes a e in e en ion compa isons. No signi ican di e ences we e ound be ween sex g oups. S uden - es o Mann–Whi ney U we e ca ied ou depending on he no mali y and Le ene es . 4. Discussion The aim o his s udy was o analyze he e ec s o a physical exe cise p og am based on concu en aining on lipoin lamma ion ma ke adipokines in adul s wi h obesi y, compa ing he esponses be ween men and women. Table 2compa es he esul s o he en i e sample (n =26), showing ha he ini ial a e age lep in le els we e 44.09 ng/mL. These le els a e associa ed wi h g ea e insulin esis ance, and hey a e usually ound in people wi h a BMI abo e 30. The esul s show an imp o emen o hese alues a e he in e en ion, om 44.09 down o 41.59 ng/mL, al hough his dec ease was small ( − 2.5 ng/mL) and no s a is ically signi ican . The changes in adiponec in we e also posi i e, ha is, he e was an inc ease in i s blood le els (+0.32 ug/mL), al hough his inc ease was no s a is ically signi ican ei he . The esul s a e p esen ed sepa a ely by sex in Tables 3and 4. These esul s a e simila o hose ob ained conside ing he en i e sample. The e we e signs o imp o emen in adiponec in and lep in, al hough such changes we e e y small. On he o he hand, he e we e mo e conside able di e ences in he inc eases in he A/L a io, which we e signi ican in he women’s g oup (p=0.5) and close o s a is ical signi icance in he men’s g oup (p=0.08), wi h a la ge e ec size in women (0.55) and mode a e in men (0.46). In nume ous s udies, people wi h obesi y ha e conduc ed di e en aining p og ams, epo ing imp o emen s in he plasma ic le els o lep in [ 37 – 40 ], wi h signi ican dec eases. Likewise, a la ge numbe o s udies ha e analyzed he e ec s o di e en physical exe cise p og ams on he concen a ions o adiponec in [41–44]. In he p esen s udy, he changes in adiponec in and lep in we e lowe , p obably due o he ac ha he in e en ion pe iod was conside ably sho e compa ed o ha o he ci ed s udies [ 37 , 42 , 45 ], o because hei in e en ions e alua ed he acu e e ec o exe cise p og ams o highe in ensi y [ 43 , 44 ]. O he s udies combined he aining wi h he adminis a ion o e gogenic o an i-in lamma o y supplemen s [41]. The imp o emen s in he le els o adiponec in and lep in, analyzed independen ly, we e no signi ican ; howe e , he A/L a io did ob ain a signi ican inc ease a e he aining pe iod (p=0.009), In . J. En i on. Res. Public Heal h 2020,17, 6168 8 o 12 wi h a la ge e ec size (0.53). The A/L a io is a bioma ke ha has been well s udied in i s ela ionship wi h lipoin lamma ion [ 16 ], and as an indica o o obesi y and me abolic isk [ 46 – 48 ]. Howe e , only ew s udies ha e analyzed he e ec o planned and con olled physical exe cise p og ams on his ma ke (A/L a io) in people wi h obesi y, and mos o hese s udies e alua ed hese wo adipocy okines independen ly [ 27 , 30 , 49 , 50 ]. All o hem epo signi ican imp o emen s a e exe cise, bo h an inc ease in adiponec in and a dec ease in lep in, which is in line wi h he esul s o he p esen s udy. A no el y o ou s udy is ha i analyses he e ec o a concu en o combined aining p og am on a speci ic lipoin lamma ion ma ke (A/L a io), ob aining signi ican imp o emen s a e 8 weeks o in e en ion. One o he ac o s in con o e sy o disag eemen wi h he scien i ic li e a u e is ela ed o he cha ac e is ics o he aining p og ams implemen ed. In his sense, mos o he s udies ha epo posi i e esul s in he le els o bo h adipokines (adiponec in and lep in) a e he exe cise p og am, ca ied ou ae obic o ca dio espi a o y ainings [ 49 , 51 – 53 ]. Few s udies ha e included esis ance aining [ 30 , 31 ], al hough concu en o combined aining p og ams a e being applied inc easingly equen ly, as hey seem o be mo e e ec i e, as was demons a ed in he cu en s udy. Ano he inding among he ob ained esul s is ela ed o he esponse o he lipoin lamma ion ma ke s analyzed based on sex. Mos s udies ha e been conduc ed wi h samples o a single gende . In a me a-analysis published in 2017, in which 28 RCTs we e included, only wo o hese ec ui ed bo h men and women in hei samples [ 27 ]. One o hese s udies only e alua ed he e ec s o exe cise on lep in and he pa icipan s we e adolescen s [ 54 ], and in ano he s udy he pa icipan s we e child en and he au ho s only e alua ed adiponec in [ 55 ]. Ano he me a-analysis published in 2018 included 22 ials wi h 2996 indi iduals. These au ho s concluded ae obic exe cise inc eased adiponec in and educed lep in le els in p ediabe ic and diabe ic adul s. Mos ials included bo h sexes, bu he e we e no compa ed men e sus women. In addi ion, he s udies, he popula ion analyzed, and he design o physical exe cise in e en ions he e ogenei y was ound [ 56 ]. Figu e 3compa es he change pe cen ages in he h ee a iables analyzed be ween men and women, clea ly showing ha sex was no a de e mining ac o in he esponse o hese adipokines o exe cise, ob aining no signi ican di e ences be ween men and women in he esponse o he aining p og am implemen ed. A cu en na a i e e iew abou he e ec s o physical ac i i y (PA) on adipokine le els in indi iduals wi h o e weigh and obesi y has analyzed app oxima ely 90 di e en in es iga ions on adipokine le els in indi iduals wi h o e weigh /obesi y we e e iewed. The esul s suppo he bene i s o exe cise ega dless o he mode ( esis ance s. ae obic), in ensi y, and coho (heal hy s. diabe es) on adipokines le els. Howe e , se e al con ounding ac o s ( equency, in ensi y, ime, and ype o exe cise) can al e he magni ude o hese e ec s [57]. A low numbe o expe imen al subjec s and he lack o a con ol g oup a e he wo majo limi a ions o his s udy. Despi e his, he p esen s udy has been able o demons a e ha a simple and a sho p og am o physical exe cise imp o es he ma ke s o lipoin lamma ion s udied and, he e o e, he in lamma o y heal h o he pa icipan s. Howe e , cau ious in e p e a ion o cu en indings is wa an ed. The e is a la ge numbe o s udies abou he e ec o exe cise on low-g ade ch onic in lamma ion; howe e , he e is also a wide me hodological a ie y, di e si y in he cha ac e is ics o he pa icipan s, and mul iple physical exe cise p og ams implemen ed wi h impo an di e ences in he cha ac e is ics o he aining loads. The e o e, i seems ob ious ha u he esea ch is s ill equi ed in his ield. 5. Conclusions The pa icipan s o his s udy s a ed wi h a low A/L a io, wi h isk o low-g ade ch onic in lamma ion. Bo h women and men imp o ed in he h ee indica o s analyzed, al hough s a is ically signi ican imp o emen s wi h a la ge e ec size in women and mode a e in men we e ob ained in A/L a io, wi h hese imp o emen s being mo e e iden when conside ing he en i e sample wi hou sex di e en ia ion. In ac , when compa ing women and men, no di e ence was ound in he esponse o he adipokines o he exe cise p og am based on sex. In . J. En i on. Res. Public Heal h 2020,17, 6168 9 o 12 Au ho Con ibu ions: Concep ualiza ion, J.A.G.-J., W.S.-C., and A.J.S.-O.; me hodology, J.A.G.-J., W.S.-C., and A.J.S.-O.; o mal analysis, J.A.G.-J.,; in es iga ion, W.S.-C. and S.L.; esou ces, J.A.G.-J. and S.L.; da a cu a ion, J.A.G.-J.; w i ing—o iginal d a p epa a ion, J.A.G.-J.; w i ing— e iew and edi ing, J.A.G.-J., W.S.-C., and A.J.S.-O.; isualiza ion, J.A.G.-J., W.S.-C., and A.J.S.-O.; p ojec adminis a ion, J.A.G.-J.; unding acquisi ion, J.A.G.-J. All au ho s ha e ead and ag eed o he published e sion o he manusc ip . Funding: This esea ch ecei ed no ex e nal unding. Acknowledgmen s: The au ho s would like o hank o he pa icipan s. Addi ionally, Se gio Lopez acknowledges he “V Own Resea ch Plan” o he Uni e si y o Se ille (VPPI-US) con ac (co ounded by he Eu opean Social Fund). Con lic s o In e es : The au ho s decla e no con lic o in e es . Re e ences 1. W.H.O. Wo ld Heal h O ganiza ion. Obesi y and O e weigh Fac Shee . 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