Genes & CellsGenes & CellsГены и КлеткиGenes and Cells2313-18292500-2562Human Stem Cells Institute37531310.23868/gc375313ReviewsНаучные обзорыReview ArticleMolecular mechanisms of obesity: a review of the most relevant gene markersМолекулярные механизмы развития ожирения: обзор наиболее актуальных генов-маркёровhttps://orcid.org/0000-0002-1688-40458046-1515KarabanovSergey Y.КарабановСергей Юрьевич
Russian Federation

Cand. Sci. (Vet.)

к.в.н.

s.karabanov@fncps.ruhttps://orcid.org/0000-0003-4298-09273423-3754ChernukhaIrina M.ЧернухаИрина Михайловна
Russian Federation

Dr. Sci. (Tech.), Professor, Academician of the Russian Academy of Sciences

д.т.н., профессор, академик РАН

imcher@inbox.ruhttps://orcid.org/0000-0001-6934-73427063-6360KibitkinaAnastasiya A.КибиткинаАнастасия Анатольевна
Russian Federation

PhD, Student

аспирант

anastasjya@list.ruhttps://orcid.org/0000-0003-3573-930X4079-2394FedulovaLiliya V.ФедуловаЛилия Вячеславовна
Russian Federation

Dr. Sci. (Tech.), Professor of the Russian Academy of Sciences

д.т.н., профессор РАН

l.fedulova@fncps.ruV.M. Gorbatov Federal Research Center for Food SystemsФедеральный научный центр пищевых систем им. В.М. Горбатова РАН300520231612202217431450205202303052023Copyright ©; 2022, Eco-VectorCopyright ©; 2022, Эко-Вектор2022Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0/https://genescells.ru/2313-1829/article/view/375313

The development of genome-wide association studies has made it possible to isolate many genes associated with obesity — one of the most common diseases in the world. For a possible correction of this process, there is a need for a more detailed study of certain genes, the expression of which can change during metabolic processes associated with obesity.

The aim of this review is to identify the most promising candidate genes for further studies of metabolic disorders associated with obesity.

Развитие полногеномных ассоциативных исследований позволило выделить множество генов, связанных с одним из самых распространённых во всем мире заболеваний — ожирением. Для возможной коррекции данной патологии существует потребность в более детальном изучении определённых генов, экспрессия которых может изменяться при метаболических процессах, связанных с ожирением.

Целью настоящего обзора послужило определение наиболее перспективных генов-кандидатов для дальнейших исследований метаболических нарушений, ассоциированных с ожирением.

gene expressionobesitymetabolic syndromewhite adipose tissuebrown adipose tissueэкспрессия геновожирениеметаболический синдромбелая жировая тканьбурая жировая тканьThe article was prepared within the framework of the research topic FNEN-2019-0008 of the state task of the Federal State Budgetary Scientific Institution “Federal Scientific Center for Food Systems named after A.I. V.M. Gorbatov” of the Russian Academy of Sciences (in the analysis of marker genes associated with obesity processes to assess therapeutic effects aimed at correcting the metabolic syndrome), as well as with the support of the Russian Science Foundation (project No. 21-76-20032) - in the analysis of a part of thermogenesis genes, also characteristic of white and brown adipose tissue.Статья подготовлена в рамках темы НИР FNEN-2019-0008 государственного задания ФГБНУ «Федеральный научный центр пищевых систем им. В.М. Горбатова» РАН (в части анализа генов-маркёров, ассоциированных с процессами ожирения, для оценки терапевтических воздействий, направленных на коррекцию метаболического синдрома), а также при поддержке Российского научного фонда (проект № 21-76-20032) — в части анализа генов термогенеза, также характерных для белой и бурой жировой ткани.Endalifer ML, Diress G. Epidemiology, predisposing factors, biomarkers, and prevention mechanism of obesity: a systematic review. J Obes. 2020;2020:6134362. doi: 10.1155/2020/6134362Endalifer M.L., Diress G. Epidemiology, predisposing factors, biomarkers, and prevention mechanism of obesity: a systematic review // J Obes. 2020. Vol. 2020, P. 6134362. doi: 10.1155/2020/6134362Loos RJF, Yeo GSH. The genetics of obesity: from discovery to biology. Nat Rev Gen. 2022;23:120–133. doi: 10.1038/s41576-021-00414-zLoos R.J.F., Yeo G.S.H. The genetics of obesity: from discovery to biology // Nat Rev Gen. 2022. Vol. 23, P. 120–133. doi: 10.1038/s41576-021-00414-zGoutzelas Y, Kontou P, Mamuris Z, et al. Meta-analysis of gene expression data in adipose tissue reveals new obesity associated genes. Gene. 2022;818:146223. doi: 10.1016/j.gene.2022.146223Goutzelas Y., Kontou P., Mamuris Z., et al. Meta-analysis of gene expression data in adipose tissue reveals new obesity associated genes // Gene. 2022. Vol. 818, P. 146223. doi: 10.1016/j.gene.2022.146223Johnson AR, Makowski L. Nutrition and metabolic correlates of obesity and inflammation: clinical considerations. J Nutr. 2015;145(5):1131S–1136S. doi: 10.3945/jn.114.200758Johnson A.R., Makowski L. Nutrition and metabolic correlates of obesity and inflammation: clinical considerations // J Nutr. 2015. Vol. 145, N 5. P. 1131S–1136S. doi: 10.3945/jn.114.200758Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006–1012. doi: 10.7326/0003-4819-151-4-200908180-00135Moher D., Liberati A., Tetzlaff J., et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement // J Clin Epidemiol. 2009. Vol. 62, N 10. P. 1006–1012. doi: 10.7326/0003-4819-151-4-200908180-00135Gunawan S, Aulia A, Soetikno V. Development of rat metabolic syndrome models: a review. Vet World. 2021;14(7):1774–1783. doi: 10.14202/vetworld.2021.1774-1783Gunawan S., Aulia A., Soetikno V. Development of rat metabolic syndrome models: a review // Vet World. 2021. Vol 14, N 7. P. 1774–1783. doi: 10.14202/vetworld.2021.1774-1783Piskunova YV, Kazantceva AY, Baklanov AV, Bazhan NM. Mutation yellow in agouti loci prevents age-related increase of skeletal muscle genes regulating free fatty acids oxidation. Vavilov Journal of Genetics and Breeding. 2018;22(2):265–272. (In Russ). doi: 10.18699/vj18.358Пискунова Ю.В., Казанцева А.Ю., Бакланов А.В., Бажан Н.М. Мутация yellow в локусе agouti устраняет возрастное повышение экспрессии генов белков, регулирующих окисление жирных кислот в мышцах у мышей // Вавиловский журнал генетики и селекции. 2018. Т. 22, № 2. С. 265–272. doi: 10.18699/vj18.358Sonne SB, Yadav R, Yin G, et al. Obesity is associated with depot-specific alterations in adipocyte DNA methylation and gene expression. Adipocyte. 2017;6(2):124–133. doi: 10.1080/21623945.2017.1320002Sonne S.B., Yadav R., Yin G., et al. Obesity is associated with depot-specific alterations in adipocyte DNA methylation and gene expression // Adipocyte. 2017. Vol. 6, N 2. P. 124–133. doi: 10.1080/21623945.2017.1320002Vatashchuk MV, Bayliak MM, Hurza VV, et al. Metabolic syndrome: lessons from rodent and drosophila models. Biomed Res Int. 2022;2022:5850507. doi: 10.1155/2022/5850507Vatashchuk M.V., Bayliak M.M., Hurza V.V., et al. Metabolic syndrome: lessons from rodent and drosophila models // Biomed Res Int. 2022. Vol. 2022, P. 5850507. doi: 10.1155/2022/5850507Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425–432. doi: 10.1038/372425a0Zhang Y., Proenca R., Maffei M., et al. Positional cloning of the mouse obese gene and its human homologue // Nature. 1994. Vol. 372, N 6505. P. 425–432. doi: 10.1038/372425a0Palmisano BT, Zhu L, Eckel RH, Stafford JM. Sex differences in lipid and lipoprotein metabolism. Mol Metab. 2018;15:45–55. doi: 10.1016/j.molmet.2018.05.008Palmisano B.T., Zhu L., Eckel R.H., Stafford J.M. Sex differences in lipid and lipoprotein metabolism // Mol Metab. 2018. Vol. 15. P. 45–55. doi: 10.1016/j.molmet.2018.05.008Bazhan NM, Iakovleva TV, Dubinina AD, Makarova EN. Impact of sex on the adaptation of adult mice to long consumption of sweet-fat diet. Vavilov Journal of genetics and Breeding. 2020;24(8):844–852. doi: 10.18699/VJ20.682Bazhan N.M., Iakovleva T.V., Dubinina A.D. Makarova E.N. Impact of sex on the adaptation of adult mice to long consumption of sweet-fat diet // Vavilov Journal of genetics and Breeding. 2020. Vol. 24, N 8. P. 844–852. doi: 10.18699/VJ20.682Macotela Y, Boucher J, Tran TT, Kahn CR. Sex and depot differences in adipocyte insulin sensitivity and glucose metabolism. Diabetes. 2009;58(4):803–812. doi: 10.2337/db08-1054Macotela Y., Boucher J., Tran T.T., Kahn C.R. Sex and depot differences in adipocyte insulin sensitivity and glucose metabolism // Diabetes. 2009. Vol. 58, N 4. P. 803–812. doi: 10.2337/db08-1054Makarova E, Kazantseva A, Dubinina A, et al. The same metabolic response to FGF21 administration in male and female obese mice is accompanied by sex-specific changes in adipose tissue gene expression. Int J Mol Sci. 2021;22(19):10561. doi: 10.3390/ijms221910561Makarova E., Kazantseva A., Dubinina A., et al. The same metabolic response to FGF21 administration in male and female obese mice is accompanied by sex-specific changes in adipose tissue gene expression // Int J Mol Sci. 2021. Vol. 22, N 19. P. 10561. doi: 10.3390/ijms221910561Grove KL, Fried SK, Greenberg AS, et al. A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice. Int J Obes (Lond). 2010;34(6):989–1000. doi: 10.1038/ijo.2010.12Grove K.L., Fried S.K., Greenberg A.S., et al. A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice // Int J Obes (Lond). 2010. Vol. 34, N 6. P. 989–1000. doi: 10.1038/ijo.2010.12Yazdi FT, Clee SM, Meyre D. Obesity genetics in mouse and human: back and forth, and back again. Peer J. 2015;3:e856. doi: 10.7717/peerj.856Yazdi F.T., Clee S.M., Meyre D. Obesity genetics in mouse and human: back and forth, and back again // Peer J. 2015. Vol. 3, P. e856. doi: 10.7717/peerj.856Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395:763–770. doi: 10.1038/27376Friedman J.M., Halaas J.L. Leptin and the regulation of body weight in mammals // Nature. 1998. Vol. 395, P. 763–770. doi: 10.1038/27376Paracchini V, Pedotti P, Taioli E. Genetics of leptin and obesity: a HuGE review. Am J Epidemiol. 2005;162(2):101–114. doi: 10.1093/aje/kwi174Paracchini V., Pedotti P., Taioli E. Genetics of leptin and obesity: a HuGE review // Am J Epidemiol. 2005. Vol. 162, N 2. P. 101–114. doi: 10.1093/aje/kwi174Lecoutre S, Oger F, Pourpe C, et al. Maternal obesity programs increased leptin gene expression in rat male offspring via epigenetic modifications in a depot-specific manner. Mol Metab. 2017;6(8):922–930. doi: 10.1016/j.molmet.2017.05.010Lecoutre S., Oger F., Pourpe C., et al. Maternal obesity programs increased leptin gene expression in rat male offspring via epigenetic modifications in a depot-specific manner // Mol Metab. 2017. Vol. 6, N 8. P. 922–930. doi: 10.1016/j.molmet.2017.05.010Babichev VN. Organization and functioning of the neuroendocrine system. Probl Endokrinol (Mosk). 2013;59(1):62–69. (In Russ). doi: 10.14341/probl201359162-69Бабичев В.Н. Организация и функционирование нейроэндокринной системы // Проблемы эндокринологии. 2013. Т. 59, № 1. С. 62–69. doi: 10.14341/probl201359162-69Toda C, Santoro A, Kim JD, Diano S. POMC neurons: from birth to death. Annu Rev Physiol. 2017;79:209–236. doi: 10.1146/annurev-physiol-022516-034110Toda C., Santoro A., Kim J.D., Diano S. POMC neurons: from birth to death // Annu Rev Physiol. 2017. Vol. 79. P. 209–236. doi: 10.1146/annurev-physiol-022516-034110Chhabra KH, Adams JM, Jones GL, et al. Reprogramming the body weight set point by a reciprocal interaction of hypothalamic leptin sensitivity and Pomc gene expression reverts extreme obesity. Mol Metab. 2016;5(10):869–881. doi: 10.1016/j.molmet.2016.07.012Chhabra K.H., Adams J.M., Jones G.L., et al. Reprogramming the body weight set point by a reciprocal interaction of hypothalamic leptin sensitivity and Pomc gene expression reverts extreme obesity // Mol Metab. 2016. Vol. 5, N 10. P. 869–881. doi: 10.1016/j.molmet.2016.07.012Lee AK, Mojtahed-Jaberi M, Kyriakou T, et al. Effect of high-fat feeding on expression of genes controlling availability of dopamine in mouse hypothalamus. Nutrition. 2010;26(4):411–422. doi: 10.1016/j.nut.2009.05.007Lee A.K., Mojtahed-Jaberi M., Kyriakou T., et al. Effect of high-fat feeding on expression of genes controlling availability of dopamine in mouse hypothalamus // Nutrition. 2010. Vol. 26, N 4. P. 411–422. doi: 10.1016/j.nut.2009.05.007Ziotopoulou M, Mantzoros CS, Hileman SM, Flier JS. Differential expression of hypothalamic neuropeptides in the early phase of diet-induced obesity in mice. Am J Physiol Endocrinol Metab. 2000;279(4):E838–E845. doi: 10.1152/ajpendo.2000.279.4.e838Ziotopoulou M., Mantzoros C.S., Hileman S.M., Flier J.S. Differential expression of hypothalamic neuropeptides in the early phase of diet-induced obesity in mice // Am J Physiol Endocrinol Metab. 2000. Vol. 279, N 4. P. E838–E845. doi: 10.1152/ajpendo.2000.279.4.e838Huang XF, Han M, South T, Storlien L. Altered levels of POMC, AgRP and MC4-R mRNA expression in the hypothalamus and other parts of the limbic system of mice prone or resistant to chronic high-energy diet-induced obesity. Brain Res. 2003;992(1):9–19. doi: 10.1016/j.brainres.2003.08.019Huang X.F., Han M., South T., Storlien L. Altered levels of POMC, AgRP and MC4-R mRNA expression in the hypothalamus and other parts of the limbic system of mice prone or resistant to chronic high-energy diet-induced obesity // Brain Res. 2003. Vol. 992, N 1. P. 9–19. doi: 10.1016/j.brainres.2003.08.019Guan XM, Yu H, Trumbauer M, et al. Induction of neuropeptide Y expression in dorsomedial hypothalamus of diet-induced obese mice. Neuroreport. 1998;9(15):3415–3419. doi: 10.1097/00001756-199810260-00015Guan X.M., Yu H., Trumbauer M., et al. Induction of neuropeptide Y expression in dorsomedial hypothalamus of diet-induced obese mice // Neuroreport. 1998. Vol. 9, N 15. P. 3415–3419. doi: 10.1097/00001756-199810260-00015Clément K, Biebermann H, Farooqi IS, et al. MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency. Nat Med. 2018;24(5):551–555. doi: 10.1530/ey.15.11.7Clément K., Biebermann H., Farooqi I.S., et al. MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency // Nat Med. 2018. Vol. 24, N 5. P. 551–555. doi: 10.1530/ey.15.11.7Vollbach H, Brandt S, Lahr G, et al. Prevalence and phenotypic characterization of MC4R variants in a large pediatric cohort. Int J Obes. 2017;41:13–22. doi: 10.1038/ijo.2016.161Vollbach H., Brandt S., Lahr G., et al. Prevalence and phenotypic characterization of MC4R variants in a large pediatric cohort // Int J Obes. 2017. Vol. 41. P. 13–22. doi: 10.1038/ijo.2016.161Huszar D, Lynch CA, Fairchild-Huntress V, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 1997;88(1):131–141. doi: 10.1016/s0092-8674(00)81865-6Huszar D., Lynch C.A., Fairchild-Huntress V., et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice // Cell. 1997. Vol. 88, N 1. P. 131–141. doi: 10.1016/s0092-8674(00)81865-6Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518:197–206. doi: 10.1038/nature14177Locke A.E., Kahali B., Berndt S.I., et al. Genetic studies of body mass index yield new insights for obesity biology // Nature. 2015. Vol. 518, P. 197–206. doi: 10.1038/nature14177Villalobos-Comparán M, Flores-Dorantes MT, Villarreal-Molina MT, et al. The FTO gene is associated with adulthood obesity in the Mexican population. Obesity. 2008;16:2296–2301. doi: 10.1038/oby.2008.367Villalobos-Comparán M., Flores-Dorantes M.T., Villarreal-Molina M.T., et al. The FTO gene is associated with adulthood obesity in the Mexican population // Obesity. 2008. Vol. 16. P. 2296–2301. doi: 10.1038/oby.2008.367Scuteri A, Sanna S, Chen WM, et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 2007;3(7):e115. doi: 10.1371/journal.pgen.0030115.eorScuteri A., Sanna S., Chen W.M., et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits // PLoS Genet. 2007. Vol. 3, N 7. e115. doi: 10.1371/journal.pgen.0030115.eorGmoshinski IV, Apryatin SA, Sharafetdinov KK, et al. Transcriptomics research in the clinical and experimental investigation of pathogenetic mechanisms of alimentary obesity. Annals of the Russian academy of medical sciences. 2018;73(3):172–180. (In Russ). doi: 10.15690/vramn973Гмошинский И.В., Апрятин С.А., Шарафетдинов Х.Х., и др. Роль транскриптомики в исследовании патогенетических механизмов алиментарного ожирения в клинике и эксперименте // Вестник Российской академии медицинских наук. 2018. Т. 73, № 3. С. 172–180. doi: 10.15690/vramn973Cecil JE, Tavendale R, Watt P, et al. An obesity associated FTO gene variant and increased energy intake in children. N Engl J Med. 2008;359:2558–2566. doi: 10.1016/s0084-3954(09)79381-9Cecil J.E., Tavendale R., Watt P., et al. An obesity associated FTO gene variant and increased energy intake in children // N Engl J Med. 2008. Vol. 359. P. 2558–2566. doi: 10.1016/s0084-3954(09)79381-9Timpson NJ, Emmett PM, Frayling TM, et al. The fat mass- and obesity-associated locus and dietary intake in children. Am J Clin Nutr. 2008;88:971–978. doi: 10.1093/ajcn/88.4.971Timpson N.J., Emmett P.M., Frayling T.M., et al. The fat mass- and obesity-associated locus and dietary intake in children // Am J Clin Nutr. 2008. Vol. 88. P. 971–978. doi: 10.1093/ajcn/88.4.971Wardle J, Llewellyn C, Sanderson S, Plomin R. The FTO gene and measured food intake in children. Int J Obes. 2009;33:42–45. doi: 10.1038/ijo.2008.174Wardle J., Llewellyn C., Sanderson S., Plomin R. The FTO gene and measured food intake in children // Int J Obes. 2009. Vol. 33. P. 42–45. doi: 10.1038/ijo.2008.174Hakanen M, Raitakari OT, Lehtimäki T, et al. FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity. J Clin Endocrinol Metab. 2009;94(4):1281–1287. doi: 10.1210/jc.2008-1199Hakanen M., Raitakari O.T., Lehtimäki T., et al. FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity // J Clin Endocrinol Metab. 2009. Vol. 94, N 4. P. 1281–1287. doi: 10.1210/jc.2008-1199Do R, Bailey SD, Desbiens K, et al. Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study. Diabetes. 2008;57(4):1147–1150. doi: 10.2337/db07-1267Do R., Bailey S.D., Desbiens K., et al. Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study // Diabetes. 2008. Vol. 57, N 4. P. 1147–1150. doi: 10.2337/db07-1267Fischer J, Koch L, Emmerling C, et al. Inactivation of the Fto gene protects from obesity. Nature. 2009;458(7240):894–898. doi: 10.1038/nature07848Fischer J., Koch L., Emmerling C., et al. Inactivation of the Fto gene protects from obesity // Nature. 2009. Vol. 458, N 7240. P. 894–898. doi: 10.1038/nature07848Church C, Lee S, Bagg EA, et al. A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene. PLoS Genet. 2009;5(8):e1000599. doi: 10.1371/journal.pgen.1000599Church C., Lee S., Bagg E.A., et al. A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene // PLoS Genet. 2009. Vol. 5, N 8. P. e1000599. doi: 10.1371/journal.pgen.1000599Church C, Moir L, McMurray F, et al. Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet. 2010;42:1086–1092. doi: 10.1038/ng.713Church C., Moir L., McMurray F., et al. Overexpression of Fto leads to increased food intake and results in obesity // Nat Genet. 2010. Vol. 42. P. 1086–1092. doi: 10.1038/ng.713Ufimtseva MA, Popov AA, Fedotova LV, et al. Psoriasis and metabolic syndrome: a review. Obesity and metabolism. 2020;17(4):369–374. (In Russ). doi: 10.14341/omet12517Уфимцева М.А., Попов А.А., Федотова Л.В., и др. Псориаз и метаболический синдром: обзор литературы // Ожирение и метаболизм. 2020. Т. 17, № 4. С. 369–374. doi: 10.14341/omet12517de Araujo TM, Razolli DS, Correa-da-Silva F, et al. The partial inhibition of hypothalamic IRX3 exacerbates obesity. EBioMedicine. 2019;39:448–460. doi: 10.1016/j.ebiom.2018.11.048de Araujo T.M., Razolli D.S., Correa-da-Silva F., et al. The partial inhibition of hypothalamic IRX3 exacerbates obesity // EBioMedicine. 2019. Vol. 39. P. 448–460. doi: 10.1016/j.ebiom.2018.11.048Dimitrijevic M, Stanojevic S, Vujic V, et al. Neuropeptide Y and its receptor subtypes specifically modulate rat peritoneal macrophage functions in vitro: counter regulation through Y1 and Y2/5 receptors. Regul Pept. 2005;124:163–172. doi: 10.1016/j.regpep.2004.07.012Dimitrijevic M., Stanojevic S., Vujic V., et al. Neuropeptide Y and its receptor subtypes specifically modulate rat peritoneal macrophage functions in vitro: counter regulation through Y1 and Y2/5 receptors // Regul Pept. 2005. Vol. 124. P. 163–172. doi: 10.1016/j.regpep.2004.07.012Singer K, Morris DL, Oatmen KE, et al. Neuropeptide Y is produced by adipose tissue macrophages and regulates obesity-induced inflammation. PLoS One. 2013;8(3):e57929. doi: 10.1371/journal.pone.0057929Singer K., Morris D.L., Oatmen K.E., et al. Neuropeptide Y is produced by adipose tissue macrophages and regulates obesity-induced inflammation // PLoS One. 2013. Vol. 8, N 3. P. e57929. doi: 10.1371/journal.pone.0057929Zhang W, Cline MA, Gilbert E.R. Hypothalamus-adipose tissue crosstalk: neuropeptide Y and the regulation of energy metabolism. Nutr Metab (Lond). 2014;11:27. doi: 10.1186/1743-7075-11-27Zhang W., Cline M.A., Gilbert, E.R. Hypothalamus-adipose tissue crosstalk: neuropeptide Y and the regulation of energy metabolism // Nutr Metab (Lond). 2014. Vol. 11. P. 27. doi: 10.1186/1743-7075-11-27Segal-Lieberman G, Trombly DJ, Juthani V, et al. NPY ablation in C57BL/6 mice leads to mild obesity and to an impaired refeeding response to fasting. Am J Physiol Endocrinol Metab. 2003;284(6):E1131–E1139. doi: 10.1152/ajpendo.00491.2002Segal-Lieberman G., Trombly D.J., Juthani V., et al. NPY ablation in C57BL/6 mice leads to mild obesity and to an impaired refeeding response to fasting // Am J Physiol Endocrinol Metab. 2003. Vol. 284, N 6. P. E1131–E1139. doi: 10.1152/ajpendo.00491.2002Zhang X, Zhang CC, Yang H, et al. An epistatic interaction between Pnpla2 and Lipe reveals new pathways of adipose tissue lipolysis. Cells. 2019;8(5):395. doi: 10.3390/cells8050395Zhang X., Zhang C.C., Yang H., et al. An epistatic interaction between Pnpla2 and Lipe reveals new pathways of adipose tissue lipolysis // Cells. 2019. Vol. 8, N 5. P. 395. doi: 10.3390/cells8050395Haemmerle G, Zimmermann R, Hayn M, et al. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J Biol Chem. 2002;277:4806–4815. doi: 10.1074/jbc.m110355200Haemmerle G., Zimmermann R., Hayn M., et al. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis // J Biol Chem. 2002. Vol. 277. P. 4806–4815. doi: 10.1074/jbc.m110355200Voshol PJ, Haemmerle G, Ouwens DM, et al. Increased hepatic insulin sensitivity together with decreased hepatic triglyceride stores in hormone-sensitive lipase-deficient mice. Endocrinology. 2003;144:3456–3462. doi: 10.1210/en.2002-0036Voshol P.J., Haemmerle G., Ouwens D.M., et al. Increased hepatic insulin sensitivity together with decreased hepatic triglyceride stores in hormone-sensitive lipase-deficient mice // Endocrinology. Vol. 2003, N 144. P. 3456–3462. doi: 10.1210/en.2002-0036Seki M, Miwa A, Ohsaka F, et al. Local free fatty acids trigger the expression of lipopolysaccharide-binding protein in murine white adipose tissue. Biosci Microbiota Food Health. 2022;41(2):54–65. doi: 10.12938/bmfh.2021-061Seki M., Miwa A., Ohsaka F., et al. Local free fatty acids trigger the expression of lipopolysaccharide-binding protein in murine white adipose tissue // Biosci Microbiota Food Health. 2022. Vol. 41, N 2. P. 54–65. doi: 10.12938/bmfh.2021-061Wang H, Eckel RH. Lipoprotein lipase: from gene to obesity. Am J Physiol Endocrinol Metab. 2009;297(2):E271–E288. doi: 10.1152/ajpendo.90920.2008Wang H., Eckel R.H. Lipoprotein lipase: from gene to obesity // Am J Physiol Endocrinol Metab. 2009. Vol. 297, N 2. P. E271–E288. doi: 10.1152/ajpendo.90920.2008Kim JK, Fillmore JJ, Chen Y, et al. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci U S A. 2001;98(13):7522–7527. doi: 10.1073/pnas.121164498Kim J.K., Fillmore J.J., Chen Y., et al. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance // Proc Natl Acad Sci U S A. 2001. Vol. 98, N 13. P. 7522–7527. doi: 10.1073/pnas.121164498Wang H, Knaub LA, Jensen DR, et al. Skeletal muscle-specific deletion of lipoprotein lipase enhances insulin signaling in skeletal muscle but causes insulin resistance in liver and other tissues. Diabetes. 2009;58:116–124. doi: 10.2337/db07-1839Wang H., Knaub L.A., Jensen D.R., et al. Skeletal muscle-specific deletion of lipoprotein lipase enhances insulin signaling in skeletal muscle but causes insulin resistance in liver and other tissues // Diabetes. 2009. Vol. 58, P. 116–124. doi: 10.2337/db07-1839Michalik L, Auwerx J, Berger JP, et al. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev. 2006;58(4):726–741. doi: 10.1124/pr.58.4.5Michalik L., Auwerx J., Berger J.P., et al. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors // Pharmacol Rev. 2006. Vol. 58, N 4. P. 726–741. doi: 10.1124/pr.58.4.5Chawla A, Repa JJ, Evans RM. Mangelsdorf DJ. Nuclear receptors and lipid physiology: opening the X-files. Science. 2001;294:1866–1870. doi: 10.1126/science.294.5548.1866Chawla A., Repa J.J., Evans R.M., Mangelsdorf D.J. Nuclear receptors and lipid physiology: opening the X-files // Science. 2001. Vol. 294. P. 1866–1870. doi: 10.1126/science.294.5548.1866Han L, Shen WJ, Bittner S, et al. PPARs: regulators of metabolism and as therapeutic targets in cardiovascular disease. Part I: PPAR-α. Future Cardiol. 2017;13(3):259–278. doi: 10.2217/fca-2016-0059Han L., Shen W.J., Bittner S., et al. PPARs: regulators of metabolism and as therapeutic targets in cardiovascular disease. Part I: PPAR-α // Future Cardiol. 2017. Vol. 13, N 3. P. 259–278. doi: 10.2217/fca-2016-0059Lazar MA. PPAR gamma, 10 years later. Biochimie. 2005;87(1):9–13. doi: 10.1016/j.biochi.2004.10.021Lazar M.A. PPAR gamma, 10 years later // Biochimie. 2005. Vol. 87, N 1. P. 9–13. doi: 10.1016/j.biochi.2004.10.021Gavrilova O, Haluzik M, Matsusue K, et al. Liver peroxisome proliferator-activated receptor γ contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass. J Biol Chem. 2003;278(36):34268–34276. doi: 10.1074/jbc.M300043200Gavrilova O., Haluzik M., Matsusue K., et al. Liver peroxisome proliferator-activated receptor γ contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass // J Biol Chem. 2003. Vol. 278, N 36. P. 34268–34276. doi: 10.1074/jbc.M300043200Soccio RE, Li Z, Chen ER, et al. Targeting PPARγ in the epigenome rescues genetic metabolic defects in mice. J Clin Invest. 2017;127(4):1451–1462. doi: 10.1172/JCI91211Soccio R.E., Li Z., Chen E.R., et al. Targeting PPARγ in the epigenome rescues genetic metabolic defects in mice // J Clin Invest. 2017. Vol. 127, N 4. P. 1451–1462. doi: 10.1172/JCI91211Afanaskina LN, Derevtsova SN, Sindeeva LV, et al. Brown adipose tissue: features of biology, participation in energy metabolism and obesity (literature review). Annals of the Russian Academy of Medical Sciences. 2020;75(4):326–330. (In Russ). doi: 10.15690/vramn1316Афанаскина Л.Н., Деревцова С.Н., Синдеева Л.В. и др. Бурая жировая ткань: особенности биологии, участие в энергетическом обмене и ожирении (обзор литературы) // Вестник Российской академии медицинских наук. 2020. Т. 75, № 4. С. 326–330. doi: 10.15690/vramn1316Slocum N, Durrant JR, Bailey D, et al. Responses of brown adipose tissue to diet-induced obesity, exercise, dietary restriction and ephedrine treatment. Exp Toxicol Pathol. 2013;65(5):549–557. doi: 10.1016/j.etp.2012.04.001Slocum N., Durrant J.R., Bailey D., et al. Responses of brown adipose tissue to diet-induced obesity, exercise, dietary restriction and ephedrine treatment // Exp Toxicol Pathol. 2013. Vol. 65, N 5. P. 549–557. doi: 10.1016/j.etp.2012.04.001Kenji I, Tetsuya Y. UCP1 dependent and independent thermogenesis in brown and beige adipocytes. Front Endocrinol (Lausanne). 2020;11:498. doi: 10.3389/fendo.2020.00498Kenji I., Tetsuya Y. UCP1 dependent and independent thermogenesis in brown and beige adipocytes // Front Endocrinol (Lausanne). 2020. Vol. 11, P. 498. doi: 10.3389/fendo.2020.00498Zhang Z, Liew CW, Handy DE, et al. High glucose inhibits glucose-6-phosphate dehydrogenase, leading to increased oxidative stress and beta-cell apoptosis. FASEB J. 2010;24:1497–1505. doi: 10.1096/fj.09-136572Zhang Z., Liew C.W., Handy D.E., et al. High glucose inhibits glucose-6-phosphate dehydrogenase, leading to increased oxidative stress and beta-cell apoptosis // FASEB J. 2010. Vol. 24, P. 1497–1505. doi: 10.1096/fj.09-136572Taubes G. Insulin resistance. Prosperity’s plague. Science. 2009;325(5938):256–260. doi: 10.1126/science.325_256Taubes G. Insulin resistance. Prosperity’s plague // Science. 2009. Vol. 325, N 5938. P. 256–260. doi: 10.1126/science.325_256Hecker PA, Mapanga RF, Kimar CP, et al. Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets. Am J Physiol Endocrinol Metab. 2012;303(8):E959–E972. doi: 10.1152/ajpendo.00202.2012Hecker P.A., Mapanga R.F., Kimar C.P., et al. Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets // Am J Physiol Endocrinol Metab. 2012. Vol. 303, N 8. P. E959–E972. doi: 10.1152/ajpendo.00202.2012Ma Y, Gao M, Sun H, Liu D. Interleukin-6 gene transfer reverses body weight gain and fatty liver in obese mice. Biochim Biophys Acta. 2015;1852(5):1001–1011. doi: 10.1016/j.bbadis.2015.01.017Ma Y., Gao M., Sun H., Liu D. Interleukin-6 gene transfer reverses body weight gain and fatty liver in obese mice // Biochim Biophys Acta. 2015. Vol. 1852, N 5. P. 1001–1011. doi: 10.1016/j.bbadis.2015.01.017Wueest S, Konrad D. The role of adipocyte-specific IL-6-type cytokine signaling in FFA and leptin release. Adipocyte. 2018;7(3):226–228. doi: 10.1080/21623945.2018.1493901Wueest S., Konrad D. The role of adipocyte-specific IL-6-type cytokine signaling in FFA and leptin release // Adipocyte. 2018. Vol. 7, N 3. P. 226–228. doi: 10.1080/21623945.2018.1493901Ather JL, Poynter ME. Serum amyloid A3 is required for normal weight and immunometabolic function in mice. PLoS One. 2018;13(2):e0192352. doi: 10.1371/journal.pone.0192352Ather J.L., Poynter M.E. Serum amyloid A3 is required for normal weight and immunometabolic function in mice // PLoS One. 2018. Vol. 13, N 2. P. e0192352. doi: 10.1371/journal.pone.0192352Sindhu S, Thomas R, Shihab P, et al. Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: significance for metabolic inflammation. PLoS One. 2015;10(7):e0133494. doi: 10.1371/journal.pone.0133494Sindhu S., Thomas R., Shihab P., et al. Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: significance for metabolic inflammation // PLoS One. 2015. Vol. 10, N 7. P. e0133494. doi: 10.1371/journal.pone.0133494Han MS, White A, Perry RJ, et al. Regulation of adipose tissue inflammation by interleukin 6. Proc Natl Acad Sci U S A. 2020;117(6):2751–2760. doi: 10.1073/pnas.1920004117Han M.S., White A., Perry R.J., et al. Regulation of adipose tissue inflammation by interleukin 6 // Proc Natl Acad Sci U S A. 2020. Vol. 117, N 6. P. 2751–2760. doi: 10.1073/pnas.1920004117Khateeb S, Albalawi A, Alkhedaide A. Regulatory effect of diosgenin on lipogenic genes expression in high-fat diet-induced obesity in mice. Saudi J Biol Sci. 2021;28(1):1026–1032. doi: 10.1016/j.sjbs.2020.11.045Khateeb S., Albalawi A., Alkhedaide A. Regulatory effect of diosgenin on lipogenic genes expression in high-fat diet-induced obesity in mice // Saudi J Biol Sci. 2021. Vol. 28, N 1. P. 1026–1032. doi: 10.1016/j.sjbs.2020.11.045Berndt J, Kovacs P, Ruschke K, et al. Fatty acid synthase gene expression in human adipose tissue: association with obesity and type 2 diabetes. Diabetologia. 2007;50:1472–1480. doi: 10.1055/s-2007-982136Berndt J., Kovacs P., Ruschke K., et al. Fatty acid synthase gene expression in human adipose tissue: association with obesity and type 2 diabetes // Diabetologia. 2007. Vol. 50, P. 1472–1480. doi: 10.1055/s-2007-982136Turner SM, Roy S, Sul HS, et al. Dissociation between adipose tissue fluxes and lipogenic gene expression in ob/ob mice. Am J Physiol Endocrinol Metab. 2007;292(4):E1101–E1109. doi: 10.1152/ajpendo.00309.2005Turner S.M., Roy S., Sul H.S., et al. Dissociation between adipose tissue fluxes and lipogenic gene expression in ob/ob mice // Am J Physiol Endocrinol Metab. 2007. Vol. 292, N 4. P. E1101–E1109. doi: 10.1152/ajpendo.00309.2005Mayas MD, Ortega FJ, Macías-González M, et al. Inverse relation between FASN expression in human adipose tissue and the insulin resistance level. Nutr Metab (Lond). 2010;7:3. doi: 10.1186/1743-7075-7-3Mayas M.D., Ortega F.J., Macías-González M., et al. Inverse relation between FASN expression in human adipose tissue and the insulin resistance level // Nutr Metab (Lond). 2010. Vol. 7. P. 3. doi: 10.1186/1743-7075-7-3Bonen A, Tandon NN, Glatz JF, et al. The fatty acid transporter FAT/CD36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes. Int J Obes (Lond). 2006;30:877–883. doi: 10.1038/sj.ijo.0803212Bonen A., Tandon N.N., Glatz J.F., et al. The fatty acid transporter FAT/CD36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes // Int J Obes (Lond). 2006. Vol. 30. P. 877–883. doi: 10.1038/sj.ijo.0803212Coburn CT, Knapp FF Jr, Febbraio M, et al. Defective uptake and utilization of long chain fatty acids in muscle and adipose tissues of CD36 knockout mice. J Biol Chem. 2000;275:32523–32529. doi: 10.1074/jbc.m003826200Coburn C.T., Knapp F.F. Jr., Febbraio M., et al. Defective uptake and utilization of long chain fatty acids in muscle and adipose tissues of CD36 knockout mice // J Biol Chem. 2000. Vol. 275. P. 32523–32529. doi: 10.1074/jbc.m003826200Hajri T, Hall AM, Jensen DR, et al. CD36-facilitated fatty acid uptake inhibits leptin production and signaling in adipose tissue. Diabetes. 2007;56:1872–1880. doi: 10.2337/db06-1699Hajri T., Hall A.M., Jensen D.R., et al. CD36-facilitated fatty acid uptake inhibits leptin production and signaling in adipose tissue // Diabetes. 2007. Vol. 56. P. 1872–1880. doi: 10.2337/db06-1699Kennedy DJ, Kuchibhotla S, Westfall KM, et al. A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling. Cardiovasc Res. 2011;89:604–613. doi: 10.1093/cvr/cvq360Kennedy D.J., Kuchibhotla S., Westfall K.M., et al. A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signaling // Cardiovasc Res. 2011. Vol. 89. P. 604–613. doi: 10.1093/cvr/cvq360Cai L, Wang Z, Ji A, et al. Scavenger receptor CD36 expression contributes to adipose tissue inflammation and cell death in diet-Induced obesity. PLoS One. 2012;7(5):e36785. doi: 10.1371/journal.pone.0036785Cai L., Wang Z., Ji A., et al. Scavenger receptor CD36 expression contributes to adipose tissue inflammation and cell death in diet-induced obesity // PLoS One. 2012. Vol. 7, N 5. P. e36785. doi: 10.1371/journal.pone.0036785