ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet201733-10ometendo-8649Research ArticleОбзор литературыReviewВисцеральное ожирение и кардиометаболический риск: особенности гормональной и иммунной регуляцииVisceral obesity and cardiometabolic risk: features of hormonal and immune regulationhttps://orcid.org/0000-0003-4537-0008КологривоваИрина ВячеславовнаKologrivovaIrina V.

кандидат медицинских наук, научный сотрудник отделения функциональной и лабораторной диагностики

Ph.D.

ikologrivova@gmail.comhttps://orcid.org/0000-0002-6489-0650ВинницкаяИрина ВладимировнаVinnitskayaIrina V.

научный сотрудник отделения атеросклероза и хронической ишемической болезни сердца

MD

irina_khor@list.ruhttps://orcid.org/0000-0002-6679-1269КошельскаяОльга АнатольевнаKoshelskayaOlga A.

доктор медицинских наук, профессор, ведущий научный сотрудник отделения атеросклероза и хронической ишемической болезни сердца

Sc.D., prof.

koshel@live.ruhttps://orcid.org/0000-0001-9645-6720СусловаТатьяна ЕвгеньевнаSuslovaTatiana E.

кандидат медицинских наук, ведущий научный сотрудник отделения функциональной и лабораторной диагностики

Ph.D.

tes@cardio-tomsk.ru<p>ФГБНУ &laquo;Томский национальный исследовательский медицинский центр Российской академии наук&raquo;, Томск</p>Россия<p>Tomsk National Research Medical Center of the Russian Academy of Sciences</p>Russian Federation201713112017143310Copyright &#x00A9; Кологривова И.В., Винницкая И.В., Кошельская О.А., Суслова Т.Е., 20172017Кологривова И.В., Винницкая И.В., Кошельская О.А., Суслова Т.Е.Kologrivova I.V., Vinnitskaya I.V., Koshelskaya O.A., Suslova T.E.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/8649

Вопрос прогностического значения ожирения в развитии сердечно-сосудистых заболеваний до сих пор остается открытым. Различный вклад висцеральной и подкожной жировой ткани в формирование кардиометаболического риска освещен во многих исследовательских работах. Данные ряда эпидемиологических исследований подтверждают связь висцерального ожирения с формированием аномального метаболического профиля и повышенным сердечно-сосудистым риском, в то время как подкожной жировой ткани приписывают относительные протективные свойства. Патофизиологические механизмы, опосредующие связь висцерального ожирения с развитием атеросклероза, остаются недостаточно изученными. Установлено, что половые гормоны, эстрогены и андрогены принимают участие в перераспределении жировой ткани, поддержании энергетического гомеостаза, оказывают влияние на секрецию адипокинов и иммунорегуляцию жировой ткани. При этом широко представленные в жировой ткани клетки иммунной системы, в том числе и адаптивного иммунитета, вносят вклад в развитие системного воспаления при ожирении и участвуют в атерогенезе. По данным последних исследований, нарушение продукции стероидных гормонов может быть взаимосвязано с развитием локального субклинического воспаления и влиять на характер кардиометаболических эффектов жировой ткани. В обзоре обсуждаются возможные механизмы, за счет которых осуществляется данная взаимосвязь и реализуется сердечно-сосудистый риск при ожирении.

The issue of the prognostic value of obesity in the development of cardiovascular diseases still remains open. Different input of visceral and subcutaneous adipose tissue in the formation of cardiometabolic risk is highlighted in many research works. A range of epidemiological studies provides data confirming relation of the visceral adiposity with abnormal metabolic profile and increased cardiovascular risk, while subcutaneous adipose tissue is attributed with relative protective properties. Pathophysiological mechanisms mediating interconnection of visceral adiposity with the development of atherosclerosis remain studied incompletely. It was stated that sex hormones, estrogens and androgens, participate in the redistribution of adipose tissue, sustenance of energy homeostasis, influence on the secretion of adipokines and immune regulation of adipose tissue. Meanwhile cells of immune system, including cells of the adaptive immunity, widely presented in adipose tissue contribute to the development of the local subclinical inflammation and influence on the features of cardiometabolic effects of adipose tissue. The review discusses possible mechanisms, by which abovementioned relationships are executed and cardiovascular risk in obesity is realized.

висцеральное ожирениеподкожное ожирениесердечно-сосудистый рискатеросклерозполовые гормоныТ-лимфоцитыадипокиныvisceral obesitysubcutaneous adipose tissuecardiovascular diseaseatherosclerosissex steroid hormonesT-lymphocytesadipokinesReferencesВОЗ. Ожирение и избыточный вес // Информационный бюллетень. – 2015. – №311. [WHO. Obesity and overweight. Fact sheet. 2015;311.] available from http://www.who.int/mediacentre/factsheets/fs311/ru/ ссылка активна на 1.09.2017ВОЗ. Ожирение и избыточный вес // Информационный бюллетень. – 2015. – №311. [WHO. Obesity and overweight. Fact sheet. 2015;311.] available from http://www.who.int/mediacentre/factsheets/fs311/ru/ ссылка активна на 1.09.2017Дедов И.И., Мельниченко Г.А., Романцова Т.И. Патогенетические аспекты ожирения // Ожирение и метаболизм. – 2004. – Т. 1. – №. 1. – С. 3–9. [Dedov II, Mel'nichenko GA, Romantsova TI. Patogeneticheskie aspekty ozhireniya. Obesity and metabolism. 2004;1(1):3–9. (In Russ)]. doi: 10.14341/2071-8713-517Дедов И.И., Мельниченко Г.А., Романцова Т.И. Патогенетические аспекты ожирения // Ожирение и метаболизм. – 2004. – Т. 1. – №. 1. – С. 3–9. [Dedov II, Mel'nichenko GA, Romantsova TI. Patogeneticheskie aspekty ozhireniya. Obesity and metabolism. 2004;1(1):3–9. (In Russ)]. doi: 10.14341/2071-8713-517Romero-Corral A, Montori VM, Somers VK, et al. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. The Lancet. 2006;368(9536):666-678. doi: 10.1016/s0140-6736(06)69251-9.Romero-Corral A, Montori VM, Somers VK, et al. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. The Lancet. 2006;368(9536):666-678. doi: 10.1016/s0140-6736(06)69251-9.Lavie CJ, Milani RV, Artham SM, et al. The Obesity Paradox, Weight Loss, and Coronary Disease. The American Journal of Medicine. 2009;122(12):1106-1114. doi: 10.1016/j.amjmed.2009.06.006.Lavie CJ, Milani RV, Artham SM, et al. The Obesity Paradox, Weight Loss, and Coronary Disease. The American Journal of Medicine. 2009;122(12):1106-1114. doi: 10.1016/j.amjmed.2009.06.006.Coutinho T, Goel K, Corrêa de Sá D, et al. Central Obesity and Survival in Subjects With Coronary Artery Disease. J Am Coll Cardiol. 2011;57(19):1877-1886. doi: 10.1016/j.jacc.2010.11.058.Coutinho T, Goel K, Corrêa de Sá D, et al. Central Obesity and Survival in Subjects With Coronary Artery Disease. J Am Coll Cardiol. 2011;57(19):1877-1886. doi: 10.1016/j.jacc.2010.11.058.Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37(29):2315-2381. doi: 10.1093/eurheartj/ehw106.Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37(29):2315-2381. doi: 10.1093/eurheartj/ehw106.Shah RV, Murthy VL, Abbasi SA, et al. Visceral Adiposity and the Risk of Metabolic Syndrome Across Body Mass Index. JACC: Cardiovascular Imaging. 2014;7(12):1221-1235. doi: 10.1016/j.jcmg.2014.07.017.Shah RV, Murthy VL, Abbasi SA, et al. Visceral Adiposity and the Risk of Metabolic Syndrome Across Body Mass Index. JACC: Cardiovascular Imaging. 2014;7(12):1221-1235. doi: 10.1016/j.jcmg.2014.07.017.Fisher FM, McTernan PG, Valsamakis G, et al. Differences in Adiponectin Protein Expression: Effect of Fat Depots and Type 2 Diabetic Status. Horm Metab Res. 2002;34(11/12):650-654. doi: 10.1055/s-2002-38246.Fisher FM, McTernan PG, Valsamakis G, et al. Differences in Adiponectin Protein Expression: Effect of Fat Depots and Type 2 Diabetic Status. Horm Metab Res. 2002;34(11/12):650-654. doi: 10.1055/s-2002-38246.McTernan PG, McTernan CL, Chetty R, et al. Increased Resistin Gene and Protein Expression in Human Abdominal Adipose Tissue. J Clin Endocr Metab. 2002;87(5):2407-2407. doi: 10.1210/jcem.87.5.8627.McTernan PG, McTernan CL, Chetty R, et al. Increased Resistin Gene and Protein Expression in Human Abdominal Adipose Tissue. J Clin Endocr Metab. 2002;87(5):2407-2407. doi: 10.1210/jcem.87.5.8627.Hiuge-Shimizu A, Kishida K, Funahashi T, et al. Coexistence of Visceral Fat and Multiple Risk Factor Accumulations is Strongly Associated with Coronary Artery Disease in Japanese (The VACATION-J Study). Journal of Atherosclerosis and Thrombosis. 2012;19(7):657-663. doi: 10.5551/jat.13037.Hiuge-Shimizu A, Kishida K, Funahashi T, et al. Coexistence of Visceral Fat and Multiple Risk Factor Accumulations is Strongly Associated with Coronary Artery Disease in Japanese (The VACATION-J Study). Journal of Atherosclerosis and Thrombosis. 2012;19(7):657-663. doi: 10.5551/jat.13037.Abazid R, Kattea M, Sayed S, et al. Visceral adipose tissue influences on coronary artery calcification at young and middle-age groups using computed tomography angiography. Avicenna Journal of Medicine. 2015;5(3):83. doi: 10.4103/2231-0770.160242.Abazid R, Kattea M, Sayed S, et al. Visceral adipose tissue influences on coronary artery calcification at young and middle-age groups using computed tomography angiography. Avicenna Journal of Medicine. 2015;5(3):83. doi: 10.4103/2231-0770.160242.Kang SJ, Kim D, Park HE, et al. Visceral adipose tissue area is associated with coronary stenosis and noncalcified plaques. Int J Obes. 2013;38(2):272-278. doi: 10.1038/ijo.2013.105.Kang SJ, Kim D, Park HE, et al. Visceral adipose tissue area is associated with coronary stenosis and noncalcified plaques. Int J Obes. 2013;38(2):272-278. doi: 10.1038/ijo.2013.105.Thörne A, Lönnqvist F, Apelman J, et al. A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding. Int J Obes. 2002;26(2):193-199. doi: 10.1038/sj.ijo.0801871.Thörne A, Lönnqvist F, Apelman J, et al. A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding. Int J Obes. 2002;26(2):193-199. doi: 10.1038/sj.ijo.0801871.Klein S, Fontana L, Young VL, et al. Absence of an Effect of Liposuction on Insulin Action and Risk Factors for Coronary Heart Disease. N Engl J Med. 2004;350(25):2549-2557. doi: 10.1056/NEJMoa033179.Klein S, Fontana L, Young VL, et al. Absence of an Effect of Liposuction on Insulin Action and Risk Factors for Coronary Heart Disease. N Engl J Med. 2004;350(25):2549-2557. doi: 10.1056/NEJMoa033179.Manolopoulos KN, Karpe F, Frayn KN. Gluteofemoral body fat as a determinant of metabolic health. Int J Obes. 2010;34(6):949-959. doi: 10.1038/ijo.2009.286.Manolopoulos KN, Karpe F, Frayn KN. Gluteofemoral body fat as a determinant of metabolic health. Int J Obes. 2010;34(6):949-959. doi: 10.1038/ijo.2009.286.Kaess BM, Pedley A, Massaro JM, et al. The ratio of visceral to subcutaneous fat, a metric of body fat distribution, is a unique correlate of cardiometabolic risk. Diabetologia. 2012;55(10):2622-2630. doi: 10.1007/s00125-012-2639-5.Kaess BM, Pedley A, Massaro JM, et al. The ratio of visceral to subcutaneous fat, a metric of body fat distribution, is a unique correlate of cardiometabolic risk. Diabetologia. 2012;55(10):2622-2630. doi: 10.1007/s00125-012-2639-5.Wildman RP, Janssen I, Khan UI, et al. Subcutaneous adipose tissue in relation to subclinical atherosclerosis and cardiometabolic risk factors in midlife women. Am J Clin Nutr. 2011;93(4):719-726. doi: 10.3945/ajcn.110.007153.Wildman RP, Janssen I, Khan UI, et al. Subcutaneous adipose tissue in relation to subclinical atherosclerosis and cardiometabolic risk factors in midlife women. Am J Clin Nutr. 2011;93(4):719-726. doi: 10.3945/ajcn.110.007153.DiTomasso D, Carnethon MR, Wright CM, Allison MA. The associations between visceral fat and calcified atherosclerosis are stronger in women than men. Atherosclerosis. 2010;208(2):531-536. doi: 10.1016/j.atherosclerosis.2009.08.015.DiTomasso D, Carnethon MR, Wright CM, Allison MA. The associations between visceral fat and calcified atherosclerosis are stronger in women than men. Atherosclerosis. 2010;208(2):531-536. doi: 10.1016/j.atherosclerosis.2009.08.015.Talman AH, Psaltis PJ, Cameron JD, et al. Epicardial adipose tissue: far more than a fat depot. Cardiovasc Diagn Ther. 2014;4(6):416–429. doi: 10.3978/j.issn.2223-3652.2014.11.05Talman AH, Psaltis PJ, Cameron JD, et al. Epicardial adipose tissue: far more than a fat depot. Cardiovasc Diagn Ther. 2014;4(6):416–429. doi: 10.3978/j.issn.2223-3652.2014.11.05Wu F-Z, Wu CC, Kuo P-L, Wu M-T. Differential impacts of cardiac and abdominal ectopic fat deposits on cardiometabolic risk stratification. BMC Cardiovasc Disord. 2016;16(1). doi: 10.1186/s12872-016-0195-5.Wu F-Z, Wu CC, Kuo P-L, Wu M-T. Differential impacts of cardiac and abdominal ectopic fat deposits on cardiometabolic risk stratification. BMC Cardiovasc Disord. 2016;16(1). doi: 10.1186/s12872-016-0195-5.Saely CH, Geiger K, Drexel H. Brown versus White Adipose Tissue: A Mini-Review. Gerontology. 2012;58(1):15-23. doi: 10.1159/000321319.Saely CH, Geiger K, Drexel H. Brown versus White Adipose Tissue: A Mini-Review. Gerontology. 2012;58(1):15-23. doi: 10.1159/000321319.Tam CS, Lecoultre V, Ravussin E. Brown Adipose Tissue: Mechanisms and Potential Therapeutic Targets. Circulation. 2012;125(22):2782-2791. doi: 10.1161/circulationaha.111.042929.Tam CS, Lecoultre V, Ravussin E. Brown Adipose Tissue: Mechanisms and Potential Therapeutic Targets. Circulation. 2012;125(22):2782-2791. doi: 10.1161/circulationaha.111.042929.Lidell ME, Betz MJ, Enerbäck S. Brown adipose tissue and its therapeutic potential. J Intern Med. 2014;276(4):364-377. doi: 10.1111/joim.12255.Lidell ME, Betz MJ, Enerbäck S. Brown adipose tissue and its therapeutic potential. J Intern Med. 2014;276(4):364-377. doi: 10.1111/joim.12255.Stevens J, Katz EG, Huxley RR. Associations between gender, age and waist circumference. Eur J Clin Nutr. 2009;64(1):6-15. doi: 10.1038/ejcn.2009.101.Stevens J, Katz EG, Huxley RR. Associations between gender, age and waist circumference. Eur J Clin Nutr. 2009;64(1):6-15. doi: 10.1038/ejcn.2009.101.Phillips GB, Jing T, Heymsfield SB. Does insulin resistance, visceral adiposity, or a sex hormone alteration underlie the metabolic syndrome? Studies in women. Metabolism. 2008;57(6):838-844. doi: 10.1016/j.metabol.2008.01.029.Phillips GB, Jing T, Heymsfield SB. Does insulin resistance, visceral adiposity, or a sex hormone alteration underlie the metabolic syndrome? Studies in women. Metabolism. 2008;57(6):838-844. doi: 10.1016/j.metabol.2008.01.029.Wang C, Jackson G, Jones TH, et al. Low Testosterone Associated With Obesity and the Metabolic Syndrome Contributes to Sexual Dysfunction and Cardiovascular Disease Risk in Men With Type 2 Diabetes. Diabetes Care. 2011;34(7):1669-1675. doi: 10.2337/dc10-2339.Wang C, Jackson G, Jones TH, et al. Low Testosterone Associated With Obesity and the Metabolic Syndrome Contributes to Sexual Dysfunction and Cardiovascular Disease Risk in Men With Type 2 Diabetes. Diabetes Care. 2011;34(7):1669-1675. doi: 10.2337/dc10-2339.Polari L, Yatkin E, Martínez Chacón MG, et al. Weight gain and inflammation regulate aromatase expression in male adipose tissue, as evidenced by reporter gene activity. Mol Cell Endocrinol. 2015;412:123-130. doi: 10.1016/j.mce.2015.06.002.Polari L, Yatkin E, Martínez Chacón MG, et al. Weight gain and inflammation regulate aromatase expression in male adipose tissue, as evidenced by reporter gene activity. Mol Cell Endocrinol. 2015;412:123-130. doi: 10.1016/j.mce.2015.06.002.Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Dermatol. 2001;45(3):S116-S124. doi: 10.1067/mjd.2001.117432.Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Dermatol. 2001;45(3):S116-S124. doi: 10.1067/mjd.2001.117432.Misso ML, Jang C, Adams J, et al. Adipose aromatase gene expression is greater in older women and is unaffected by postmenopausal estrogen therapy. Menopause. 2005;12(2):210-215. doi: 10.1097/00042192-200512020-00016.Misso ML, Jang C, Adams J, et al. Adipose aromatase gene expression is greater in older women and is unaffected by postmenopausal estrogen therapy. Menopause. 2005;12(2):210-215. doi: 10.1097/00042192-200512020-00016.Docanto MM, Yang F, Callaghan B, et al. Ghrelin and des-acyl ghrelin inhibit aromatase expression and activity in human adipose stromal cells: suppression of cAMP as a possible mechanism. Breast Cancer Res Treat. 2014;147(1):193-201. doi: 10.1007/s10549-014-3060-1.Docanto MM, Yang F, Callaghan B, et al. Ghrelin and des-acyl ghrelin inhibit aromatase expression and activity in human adipose stromal cells: suppression of cAMP as a possible mechanism. Breast Cancer Res Treat. 2014;147(1):193-201. doi: 10.1007/s10549-014-3060-1.Al-Qahtani SM, Bryzgalova G, Valladolid-Acebes I, et al. 17β-Estradiol suppresses visceral adipogenesis and activates brown adipose tissue-specific gene expression. Horm Mol Biol Clin Investig. 2016;0(0). doi: 10.1515/hmbci-2016-0031.Al-Qahtani SM, Bryzgalova G, Valladolid-Acebes I, et al. 17β-Estradiol suppresses visceral adipogenesis and activates brown adipose tissue-specific gene expression. Horm Mol Biol Clin Investig. 2016;0(0). doi: 10.1515/hmbci-2016-0031.Sinchak K, Wagner EJ. Estradiol signaling in the regulation of reproduction and energy balance. Front Neuroendocrinol. 2012;33(4):342-363. doi: 10.1016/j.yfrne.2012.08.004.Sinchak K, Wagner EJ. Estradiol signaling in the regulation of reproduction and energy balance. Front Neuroendocrinol. 2012;33(4):342-363. doi: 10.1016/j.yfrne.2012.08.004.Gormsen LC, Host C, Hjerrild BE, et al. Estradiol acutely inhibits whole body lipid oxidation and attenuates lipolysis in subcutaneous adipose tissue: a randomized, placebo-controlled study in postmenopausal women. European Journal of Endocrinology. 2012;167(4):543-551. doi: 10.1530/eje-12-0422.Gormsen LC, Host C, Hjerrild BE, et al. Estradiol acutely inhibits whole body lipid oxidation and attenuates lipolysis in subcutaneous adipose tissue: a randomized, placebo-controlled study in postmenopausal women. European Journal of Endocrinology. 2012;167(4):543-551. doi: 10.1530/eje-12-0422.Abeles EdG, Cordeiro LMdS, Martins AdS, et al. Estrogen therapy attenuates adiposity markers in spontaneously hypertensive rats. Metabolism. 2012;61(8):1100-1107. doi: 10.1016/j.metabol.2011.12.015.Abeles EdG, Cordeiro LMdS, Martins AdS, et al. Estrogen therapy attenuates adiposity markers in spontaneously hypertensive rats. Metabolism. 2012;61(8):1100-1107. doi: 10.1016/j.metabol.2011.12.015.Stubbins RE, Najjar K, Holcomb VB, et al. Oestrogen alters adipocyte biology and protects female mice from adipocyte inflammation and insulin resistance. Diabetes, Obesity and Metabolism. 2012;14(1):58-66. doi: 10.1111/j.1463-1326.2011.01488.x.Stubbins RE, Najjar K, Holcomb VB, et al. Oestrogen alters adipocyte biology and protects female mice from adipocyte inflammation and insulin resistance. Diabetes, Obesity and Metabolism. 2012;14(1):58-66. doi: 10.1111/j.1463-1326.2011.01488.x.Barton M, Prossnitz ER. Emerging roles of GPER in diabetes and atherosclerosis. Trends Endocrinol Metab. 2015;26(4):185-192. doi: 10.1016/j.tem.2015.02.003.Barton M, Prossnitz ER. Emerging roles of GPER in diabetes and atherosclerosis. Trends Endocrinol Metab. 2015;26(4):185-192. doi: 10.1016/j.tem.2015.02.003.Fagman JB, Wilhelmson AS, Motta BM, et al. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice. The FASEB Journal. 2014;29(4):1540-1550. doi: 10.1096/fj.14-259234.Fagman JB, Wilhelmson AS, Motta BM, et al. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice. The FASEB Journal. 2014;29(4):1540-1550. doi: 10.1096/fj.14-259234.Feuerer M, Herrero L, Cipolletta D, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15(8):930-939. doi: 10.1038/nm.2002.Feuerer M, Herrero L, Cipolletta D, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15(8):930-939. doi: 10.1038/nm.2002.Moser M, Chen Y, Tian J, et al. Adipose Tissue Dendritic Cells Enhances Inflammation by Prompting the Generation of Th17 Cells. PLoS One. 2014;9(3):e92450. doi: 10.1371/journal.pone.0092450.Moser M, Chen Y, Tian J, et al. Adipose Tissue Dendritic Cells Enhances Inflammation by Prompting the Generation of Th17 Cells. PLoS One. 2014;9(3):e92450. doi: 10.1371/journal.pone.0092450.Cipolletta D. Adipose tissue-resident regulatory T cells: phenotypic specialization, functions and therapeutic potential. Immunology. 2014;142(4):517-525. doi: 10.1111/imm.12262.Cipolletta D. Adipose tissue-resident regulatory T cells: phenotypic specialization, functions and therapeutic potential. Immunology. 2014;142(4):517-525. doi: 10.1111/imm.12262.Brooks-Worrell B, Narla R, Palmer JP. Biomarkers and immune-modulating therapies for Type 2 diabetes. Trends Immunol. 2012;33(11):546-553. doi: 10.1016/j.it.2012.07.002.Brooks-Worrell B, Narla R, Palmer JP. Biomarkers and immune-modulating therapies for Type 2 diabetes. Trends Immunol. 2012;33(11):546-553. doi: 10.1016/j.it.2012.07.002.Lee B-C, Lee J. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease. 2014;1842(3):446-462. doi: 10.1016/j.bbadis.2013.05.017.Lee B-C, Lee J. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease. 2014;1842(3):446-462. doi: 10.1016/j.bbadis.2013.05.017.Weaver CT, Hatton RD. Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective. Nature Reviews Immunology. 2009;9(12):883-889. doi: 10.1038/nri2660.Weaver CT, Hatton RD. Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective. Nature Reviews Immunology. 2009;9(12):883-889. doi: 10.1038/nri2660.Eljaafari A, Robert M, Chehimi M, et al. Adipose Tissue–Derived Stem Cells From Obese Subjects Contribute to Inflammation and Reduced Insulin Response in Adipocytes Through Differential Regulation of the Th1/Th17 Balance and Monocyte Activation. Diabetes. 2015;64(7):2477-2488. doi: 10.2337/db15-0162.Eljaafari A, Robert M, Chehimi M, et al. Adipose Tissue–Derived Stem Cells From Obese Subjects Contribute to Inflammation and Reduced Insulin Response in Adipocytes Through Differential Regulation of the Th1/Th17 Balance and Monocyte Activation. Diabetes. 2015;64(7):2477-2488. doi: 10.2337/db15-0162.Pandolfi JB, Ferraro AA, Sananez I, et al. ATP-Induced Inflammation Drives Tissue-Resident Th17 Cells in Metabolically Unhealthy Obesity. The Journal of Immunology. 2016;196(8):3287-3296. doi: 10.4049/jimmunol.1502506.Pandolfi JB, Ferraro AA, Sananez I, et al. ATP-Induced Inflammation Drives Tissue-Resident Th17 Cells in Metabolically Unhealthy Obesity. The Journal of Immunology. 2016;196(8):3287-3296. doi: 10.4049/jimmunol.1502506.Subbaramaiah K, Howe LR, Bhardwaj P, et al. Obesity Is Associated with Inflammation and Elevated Aromatase Expression in the Mouse Mammary Gland. Cancer Prevention Research. 2011;4(3):329-346. doi: 10.1158/1940-6207.capr-10-0381.Subbaramaiah K, Howe LR, Bhardwaj P, et al. Obesity Is Associated with Inflammation and Elevated Aromatase Expression in the Mouse Mammary Gland. Cancer Prevention Research. 2011;4(3):329-346. doi: 10.1158/1940-6207.capr-10-0381.Luo CY, Wang L, Sun C, Li DJ. Estrogen enhances the functions of CD4+CD25+Foxp3+ regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro. Cellular and Molecular Immunology. 2010;8(1):50-58. doi: 10.1038/cmi.2010.54.Luo CY, Wang L, Sun C, Li DJ. Estrogen enhances the functions of CD4+CD25+Foxp3+ regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro. Cellular and Molecular Immunology. 2010;8(1):50-58. doi: 10.1038/cmi.2010.54.McKarns S. Selective deletion of estrogen receptor alpha in FoxP3+ CD4+ T cells influences peripheral T cell homeostasis. J Immunol, 2015;194(1 Supplement):184.21McKarns S. Selective deletion of estrogen receptor alpha in FoxP3+ CD4+ T cells influences peripheral T cell homeostasis. J Immunol, 2015;194(1 Supplement):184.21Chen R-Y, Fan Y-M, Zhang Q, et al. Estradiol Inhibits Th17 Cell Differentiation through Inhibition ofRORγTTranscription by Recruiting the ERα/REA Complex to Estrogen Response Elements of theRORγTPromoter. The Journal of Immunology. 2015;194(8):4019-4028. doi: 10.4049/jimmunol.1400806.Chen R-Y, Fan Y-M, Zhang Q, et al. Estradiol Inhibits Th17 Cell Differentiation through Inhibition ofRORγTTranscription by Recruiting the ERα/REA Complex to Estrogen Response Elements of theRORγTPromoter. The Journal of Immunology. 2015;194(8):4019-4028. doi: 10.4049/jimmunol.1400806.Walecki M, Eisel F, Klug J, et al. Androgen receptor modulates Foxp3 expression in CD4+CD25+Foxp3+ regulatory T-cells. Mol Biol Cell. 2015;26(15):2845-2857. doi: 10.1091/mbc.E14-08-1323.Walecki M, Eisel F, Klug J, et al. Androgen receptor modulates Foxp3 expression in CD4+CD25+Foxp3+ regulatory T-cells. Mol Biol Cell. 2015;26(15):2845-2857. doi: 10.1091/mbc.E14-08-1323.Arredouani MS. New insights into androgenic immune regulation. OncoImmunology. 2014;3(9):e954968. doi: 10.4161/21624011.2014.954968.Arredouani MS. New insights into androgenic immune regulation. OncoImmunology. 2014;3(9):e954968. doi: 10.4161/21624011.2014.954968.Chalubinski M, Luczak E, Wojdan K, et al. Innate lymphoid cells type 2 – emerging immune regulators of obesity and atherosclerosis. Immunol Lett. 2016;179:43-46. doi: 10.1016/j.imlet.2016.09.007.Chalubinski M, Luczak E, Wojdan K, et al. Innate lymphoid cells type 2 – emerging immune regulators of obesity and atherosclerosis. Immunol Lett. 2016;179:43-46. doi: 10.1016/j.imlet.2016.09.007.Kasahara K, Sasaki N, Yamashita T, et al. CD3 Antibody and IL-2 Complex Combination Therapy Inhibits Atherosclerosis by Augmenting a Regulatory Immune Response. Journal of the American Heart Association. 2014;3(2):e000719-e000719. doi: 10.1161/jaha.113.000719.Kasahara K, Sasaki N, Yamashita T, et al. CD3 Antibody and IL-2 Complex Combination Therapy Inhibits Atherosclerosis by Augmenting a Regulatory Immune Response. Journal of the American Heart Association. 2014;3(2):e000719-e000719. doi: 10.1161/jaha.113.000719.De Rosa V, Procaccini C, Calì G, et al. A Key Role of Leptin in the Control of Regulatory T Cell Proliferation. Immunity. 2007;26(2):241-255. doi: 10.1016/j.immuni.2007.01.011.De Rosa V, Procaccini C, Calì G, et al. A Key Role of Leptin in the Control of Regulatory T Cell Proliferation. Immunity. 2007;26(2):241-255. doi: 10.1016/j.immuni.2007.01.011.Jung MY, Kim HS, Hong HJ, et al. Adiponectin Induces Dendritic Cell Activation via PLC /JNK/NF- B Pathways, Leading to Th1 and Th17 Polarization. The Journal of Immunology. 2012;188(6):2592-2601. doi: 10.4049/jimmunol.1102588.Jung MY, Kim HS, Hong HJ, et al. Adiponectin Induces Dendritic Cell Activation via PLC /JNK/NF- B Pathways, Leading to Th1 and Th17 Polarization. The Journal of Immunology. 2012;188(6):2592-2601. doi: 10.4049/jimmunol.1102588.Chen X, Van Sinderen ML, Steinberg GR, et al. Effects of Estrogens on Adipokines and Glucose Homeostasis in Female Aromatase Knockout Mice. PLoS One. 2015;10(8):e0136143. doi: 10.1371/journal.pone.0136143.Chen X, Van Sinderen ML, Steinberg GR, et al. Effects of Estrogens on Adipokines and Glucose Homeostasis in Female Aromatase Knockout Mice. PLoS One. 2015;10(8):e0136143. doi: 10.1371/journal.pone.0136143.Tao Y, Juan LI, Wei-Gang Z, et al. Effects of Estrogen on Insulin Sensitivity and Adipokines in Mice. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2015;37(3):269–273. doi: 10.3881/j.issn.1000-503X.2015.03.004Tao Y, Juan LI, Wei-Gang Z, et al. Effects of Estrogen on Insulin Sensitivity and Adipokines in Mice. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2015;37(3):269–273. doi: 10.3881/j.issn.1000-503X.2015.03.004Gao Q, Mezei G, Nie Y, et al. Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nat Med. 2006;13(1):89-94. doi: 10.1038/nm1525.Gao Q, Mezei G, Nie Y, et al. Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nat Med. 2006;13(1):89-94. doi: 10.1038/nm1525.Nishizawa H, Shimomura I, Kishida K, et al. Androgens Decrease Plasma Adiponectin, an Insulin-Sensitizing Adipocyte-Derived Protein. Diabetes. 2002;51(9):2734-2741. doi: 10.2337/diabetes.51.9.2734.Nishizawa H, Shimomura I, Kishida K, et al. Androgens Decrease Plasma Adiponectin, an Insulin-Sensitizing Adipocyte-Derived Protein. Diabetes. 2002;51(9):2734-2741. doi: 10.2337/diabetes.51.9.2734.

The authors declare that there are no conflicts of interest present.