aterosklerozАтеросклерозAteroscleroz2078-256X2949-3633НИИТПМ-филиал ИЦиГ СО РАН10.15372/ATER20190107ateroskleroz-201Research ArticleОБЗОРЫREVIEWSИНСУЛИН И ЛЕПТИН: СПОРНЫЕ И НЕРЕШЕННЫЕ ВОПРОСЫ ИХ ВЗАИМОДЕЙСТВИЯINSULIN AND LEPTIN: DISPUTABLE AND UNSOLVED QUESTIONS OF THEIR INTERACTIONБеликЕ. В.BelikE. V.

650002, г. Кемерово, Сосновый бульвар, 6

650002, Kemerovo, Sosnovy blvd., 6

ГруздеваО. В.GruzdevaO. V.

650002, г. Кемерово, Сосновый бульвар, 6; 650056, г. Кемерово, ул. Ворошилова, 22а

650002, Kemerovo, Sosnovy blvd., 6; 650056, Kemerovo, Voroshilov str., 22а

ПаличеваЕ. И.PalichevaE. I.

650002, г. Кемерово, Сосновый бульвар, 6; 650056, г. Кемерово, ул. Ворошилова, 22а

650002, Kemerovo, Sosnovy blvd., 6; 650056, Kemerovo, Voroshilov str., 22а

ФГБНУ НИИ комплексных проблем сердечно-сосудистых заболеванийРоссияScientific Research Institute for Complex Issues of Cardiovascular DiseasesRussian FederationФГБНУ НИИ комплексных проблем сердечно-сосудистых заболеваний; ФГБОУ ВО Кемеровский государственный медицинский университет Минздрава РоссииРоссияScientific Research Institute for Complex Issues of Cardiovascular Diseases; Kemerovo State Medical University of Minzdrav of RussiaRussian Federation2019221220191514957Copyright © Белик Е.В., Груздева О.В., Паличева Е.И., 20192019Белик Е.В., Груздева О.В., Паличева Е.И.Belik E.V., Gruzdeva O.V., Palicheva E.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://ateroskleroz.elpub.ru/jour/article/view/201

Лептин и его рецептор широко распространены главным образом в белой жировой ткани. Концентрация лептина в сыворотке крови коррелирует с индексом массы тела и снижается при голодании. Инсулин, по-видимому, увеличивает экспрессию мРНК и белка лептина, а также его высвобождение адипоцитами, причем синтезированного как предварительно, так и de novo, и снижает уровень адипонектина и его рецепторов. Согласно литературным данным, хроническая гиперинсулинемия повышает содержание лептина. В настоящем обзоре обобщены последние знания о влиянии инсулина на синтез и секрецию лептина, представлены клеточные механизмы, контролирующие его синтез и высвобождение белой жировой тканью.

Leptin and its receptor are widely distributed mainly in white adipose tissue. Serum leptin concentration correlates with body mass index, and its levels decrease with fasting. Insulin appears to increase leptin mRNA and protein expression, as well as release by adipocytes, synthesized both in advance and de novo, and reduces the levels of adiponectin and its receptors. According to the literature, chronic hyperinsulinemia increases leptin levels. This review summarizes the latest knowledge on the effect of insulin on leptin synthesis and secretion; cellular mechanisms that control the synthesis and release of white adipose tissue are presented.

лептининсулинадипоцитыожирениеинсулинорезистентностьleptininsulinadipocytesobesityinsulin resistanceReferencesLi Y., Ding L., Hassan W., Abdelkader D., Shang J. Adipokines and hepatic insulin resistance // J. Diabetes Res. 2013. Vol. 2013. ID 170532.Li Y., Ding L., Hassan W., Abdelkader D., Shang J. Adipokines and hepatic insulin resistance // J. Diabetes Res. 2013. Vol. 2013. ID 170532.Rabe K., Lehrke M., Parhofer K.G., Broedl U.C. Adipokines and insulin resistance // Mol. Med. 2008. Vol. 14. P. 741–751.Rabe K., Lehrke M., Parhofer K.G., Broedl U.C. Adipokines and insulin resistance // Mol. Med. 2008. Vol. 14. P. 741–751.Белик Е.В., Груздева О.В., Каретникова В.Н., Учасова Е.Г., Дылева Ю.А., Кузьмина А.А., Шурыгина Е.А. Лептин-растворимый рецептор и провоспалительные факторы при инфаркте миокарда // Клин. медицина. 2015. Т. 93, N 5. С. 56–61.Белик Е.В., Груздева О.В., Каретникова В.Н., Учасова Е.Г., Дылева Ю.А., Кузьмина А.А., Шурыгина Е.А. Лептин-растворимый рецептор и провоспалительные факторы при инфаркте миокарда // Клин. медицина. 2015. Т. 93, N 5. С. 56–61.Отт А.В., Чумакова Г.А. Эпикардиальное ожирение как один из основных критериев метаболически тучного фенотипа ожирения и предикторов субклинического атеросклероза // Комплекс. пробл. серд.-сосуд. заболеваний. 2018. Т. 7, N 1. С. 21–28.Отт А.В., Чумакова Г.А. Эпикардиальное ожирение как один из основных критериев метаболически тучного фенотипа ожирения и предикторов субклинического атеросклероза // Комплекс. пробл. серд.-сосуд. заболеваний. 2018. Т. 7, N 1. С. 21–28.Wahlen K., Sjolin E., Lofgren P. Role of fat cell size for plasma leptin in a large population based sample // Exp. Clin. Endocrinol. Diabetes. 2011. Vol. 119. P. 291–294.Wahlen K., Sjolin E., Lofgren P. Role of fat cell size for plasma leptin in a large population based sample // Exp. Clin. Endocrinol. Diabetes. 2011. Vol. 119. P. 291–294.Fruhbeck G. Intracellular signalling pathways activated by leptin // Biochem. J. 2006. Vol. 393. P. 7–20.Fruhbeck G. Intracellular signalling pathways activated by leptin // Biochem. J. 2006. Vol. 393. P. 7–20.Yadav A., Kataria M.A., Saini V. Role of leptin and adiponectin in insulin resistance // Clin. Chim. Acta. 2013. Vol. 417. P. 80–84.Yadav A., Kataria M.A., Saini V. Role of leptin and adiponectin in insulin resistance // Clin. Chim. Acta. 2013. Vol. 417. P. 80–84.Marques-Oliveira G.H., Silva T.M., Lima W.G., Chaves V.E. Insulin as a hormone regulator of the synthesis and release of leptin by white adipose tissue // Peptides. 2018. Vol. 106. P. 49–58.Marques-Oliveira G.H., Silva T.M., Lima W.G., Chaves V.E. Insulin as a hormone regulator of the synthesis and release of leptin by white adipose tissue // Peptides. 2018. Vol. 106. P. 49–58.Perez-Suarez I., Ponce-Gonzalez J.G., de la CalleHerrero J., Losa-Reyna J., Martin-Rincon M., Morales-Alamo D., Santana A., Holmberg H.C., Calbet J.A.L. Severe energy deficit up-regulates leptin receptors, leptin signaling and PTP1B in human skeletal muscle // J. Appl. Physiol. 2017. Vol. 1235. P. 1276–1287.Perez-Suarez I., Ponce-Gonzalez J.G., de la CalleHerrero J., Losa-Reyna J., Martin-Rincon M., Morales-Alamo D., Santana A., Holmberg H.C., Calbet J.A.L. Severe energy deficit up-regulates leptin receptors, leptin signaling and PTP1B in human skeletal muscle // J. Appl. Physiol. 2017. Vol. 1235. P. 1276–1287.Aronis K.N., Diakopoulos K.N., Fiorenza C.G., Chamberland J.P., Mantzoros C.S. Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans // Diabetologia. 2011. Vol. 54. P. 2358–2367.Aronis K.N., Diakopoulos K.N., Fiorenza C.G., Chamberland J.P., Mantzoros C.S. Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans // Diabetologia. 2011. Vol. 54. P. 2358–2367.Deck C.A., Honeycutt J.L., Cheung E., Reynolds H.M., Borski R.J. Assessing the functional role of leptin in energy homeostasis and the stress response in vertebrates // Front. Endocrinol. 2017. Vol. 8. ID 63.Deck C.A., Honeycutt J.L., Cheung E., Reynolds H.M., Borski R.J. Assessing the functional role of leptin in energy homeostasis and the stress response in vertebrates // Front. Endocrinol. 2017. Vol. 8. ID 63.Chaves V.E., Frasson D., Kawashita N.H. Several agents and pathways regulate lipolysis in adipocytes // Biochimie. 2011. Vol. 93, N 10. P. 1631–1640.Chaves V.E., Frasson D., Kawashita N.H. Several agents and pathways regulate lipolysis in adipocytes // Biochimie. 2011. Vol. 93, N 10. P. 1631–1640.Niswender K.D., Magnuson M.A. Obesity and the beta cell: lessons from leptin // J. Clin. Invest. 2007. Vol. 117, N 10. P. 2753–2756.Niswender K.D., Magnuson M.A. Obesity and the beta cell: lessons from leptin // J. Clin. Invest. 2007. Vol. 117, N 10. P. 2753–2756.Reis B.S., Lee K., Fanok M.H., Mascaraque C., Amoury M., Cohn L.B., Rogoz A., Dallner O.S., Moraes-Vieira P.M., Domingos A.I., Mucida D. Leptin receptor signaling in T cells is required for Th17 differentiation // J. Immunol. 2015. Vol. 194, N 11. Р. 5253–5260.Reis B.S., Lee K., Fanok M.H., Mascaraque C., Amoury M., Cohn L.B., Rogoz A., Dallner O.S., Moraes-Vieira P.M., Domingos A.I., Mucida D. Leptin receptor signaling in T cells is required for Th17 differentiation // J. Immunol. 2015. Vol. 194, N 11. Р. 5253–5260.Messenger S.A., Moreau J.M., Ciriello J. Intermittent hypoxia and systemic leptin administration induces pSTAT3 and Fos/Fra-1 in the carotid body // Brain Res. 2012. Vol. 1446. Р. 56–70.Messenger S.A., Moreau J.M., Ciriello J. Intermittent hypoxia and systemic leptin administration induces pSTAT3 and Fos/Fra-1 in the carotid body // Brain Res. 2012. Vol. 1446. Р. 56–70.Ramos-Lobo A.M., Donato J. The role of leptin in health and disease // Temperature. 2017. Vol. 4, N 3. Р. 258–291.Ramos-Lobo A.M., Donato J. The role of leptin in health and disease // Temperature. 2017. Vol. 4, N 3. Р. 258–291.Friedman J. The long road to leptin // J. Clin. Invest. 2016. Vol. 126, N 12. Р. 4727–4734.Friedman J. The long road to leptin // J. Clin. Invest. 2016. Vol. 126, N 12. Р. 4727–4734.Mueller W.M., Stanhope K.L., Gregoire F., Evans J.L., Havel P.J. Effects of metformin and vanadium on leptin secretion from cultured rat adipocytes // Obes. Res. 2000. Vol. 8. Р. 530–539.Mueller W.M., Stanhope K.L., Gregoire F., Evans J.L., Havel P.J. Effects of metformin and vanadium on leptin secretion from cultured rat adipocytes // Obes. Res. 2000. Vol. 8. Р. 530–539.Wellhoener P., Fruehwald-Schultes B., Kern W., Dantz D., Kerner W., Born J., Fehm H.L., Peters A. Glucose metabolism rather than insulin is a main determinant of leptin secretion in humans // J. Clin. Endocrinol. Metab. 2000. Vol. 85. Р. 1267–1271.Wellhoener P., Fruehwald-Schultes B., Kern W., Dantz D., Kerner W., Born J., Fehm H.L., Peters A. Glucose metabolism rather than insulin is a main determinant of leptin secretion in humans // J. Clin. Endocrinol. Metab. 2000. Vol. 85. Р. 1267–1271.Guerci B., Hadjadj S., Quilliot D., Ziegler O., Drouin P. No acute response of leptin to an oral fat load in obese patients and during circadian rhythm in healthy controls // Eur. J. Endocrinol. 2000. Vol. 143. Р. 649–655.Guerci B., Hadjadj S., Quilliot D., Ziegler O., Drouin P. No acute response of leptin to an oral fat load in obese patients and during circadian rhythm in healthy controls // Eur. J. Endocrinol. 2000. Vol. 143. Р. 649–655.Faraj M., Havel P.J., Phelis S., Blank D., Sniderman A., Cianflone K. Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects // J. Clin. Endocrinol. Metab. 2003. Vol. 88. Р. 1594–1602.Faraj M., Havel P.J., Phelis S., Blank D., Sniderman A., Cianflone K. Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects // J. Clin. Endocrinol. Metab. 2003. Vol. 88. Р. 1594–1602.Otukonyong E.E., Dube M.G., Torto R.Kalra P., Kalra S. High-fat diet-induced ultradian leptin and insulin hypersecretion are absent in obesity-resistant rats // Obes. Res. 2005. Vol. 13. Р. 991–999.Otukonyong E.E., Dube M.G., Torto R.Kalra P., Kalra S. High-fat diet-induced ultradian leptin and insulin hypersecretion are absent in obesity-resistant rats // Obes. Res. 2005. Vol. 13. Р. 991–999.Carlson J.J., Turpin A.A., Wiebke G., Hunt S., Adam T. Pre- and post- prandial appetite hormone levels in normal weight and severely obese women // Nutr. Metab. (Lond.). 2009. Vol. 6. ID 32.Carlson J.J., Turpin A.A., Wiebke G., Hunt S., Adam T. Pre- and post- prandial appetite hormone levels in normal weight and severely obese women // Nutr. Metab. (Lond.). 2009. Vol. 6. ID 32.Laferrere B., Caixas A., Fried S.K., Bashore C., Kim J., Pi-Sunyer F.X. A pulse of insulin and dexamethasone stimulates serum leptin in fasting human subjects // Eur J. Endocrinol. 2002. Vol. 146, N 6. Р. 839–845.Laferrere B., Caixas A., Fried S.K., Bashore C., Kim J., Pi-Sunyer F.X. A pulse of insulin and dexamethasone stimulates serum leptin in fasting human subjects // Eur J. Endocrinol. 2002. Vol. 146, N 6. Р. 839–845.Stefan N., Fritsche A., Haring H., Stumvoll M. Acute stimulation of leptin concentrations in humans during hyperglycemic hyperinsulinemia. Influence of free fatty acids and fasting // Int. J. Obes. Relat. Metab. Disord. 2001. Vol. 25, N 1. Р. 138–142.Stefan N., Fritsche A., Haring H., Stumvoll M. Acute stimulation of leptin concentrations in humans during hyperglycemic hyperinsulinemia. Influence of free fatty acids and fasting // Int. J. Obes. Relat. Metab. Disord. 2001. Vol. 25, N 1. Р. 138–142.Katz L.E., Abraham M., Johansen L., Jawad A.F. Leptin levels decline steadily during prolonged fasting in lean children // J. Pediatr. 2006. Vol. 149, N 6. Р. 798–802.Katz L.E., Abraham M., Johansen L., Jawad A.F. Leptin levels decline steadily during prolonged fasting in lean children // J. Pediatr. 2006. Vol. 149, N 6. Р. 798–802.Askari H., Liu J., Dagogo-Jack S. Hormonal regulation of human leptin in vivo: effects of hydrocortisone and insulin // Int. J. Obes. Relat. Metab. Disord. 2000. Vol. 24, N 10. Р. 1254–1259.Askari H., Liu J., Dagogo-Jack S. Hormonal regulation of human leptin in vivo: effects of hydrocortisone and insulin // Int. J. Obes. Relat. Metab. Disord. 2000. Vol. 24, N 10. Р. 1254–1259.Fruehwald-Schultes B., Oltmanns K.M., Kern W., Born J., Fehm H.L., Peters A. The effect of experimentally induced insulin resistance on the leptin response to hyperinsulinaemia // Int. J. Obes. Relat. Metab. Disord. 2002. Vol. 26, N 4. Р. 510–516.Fruehwald-Schultes B., Oltmanns K.M., Kern W., Born J., Fehm H.L., Peters A. The effect of experimentally induced insulin resistance on the leptin response to hyperinsulinaemia // Int. J. Obes. Relat. Metab. Disord. 2002. Vol. 26, N 4. Р. 510–516.Norman D., Isidori A.M., Frajese V., Caprio M., Chew S.L., Grossman A.B., Clark A.J., Michael Besser G., Fabbri A. ACTH and alpha-MSH inhibit leptin expression and secretion in 3T3-L1 adipocytes: Model for a central-peripheral melanocortin-leptin pathway // Mol. Cell. Endocrinol. 2003. Vol. 200. Р. 99–109.Norman D., Isidori A.M., Frajese V., Caprio M., Chew S.L., Grossman A.B., Clark A.J., Michael Besser G., Fabbri A. ACTH and alpha-MSH inhibit leptin expression and secretion in 3T3-L1 adipocytes: Model for a central-peripheral melanocortin-leptin pathway // Mol. Cell. Endocrinol. 2003. Vol. 200. Р. 99–109.Zeigerer A., Rodeheffer M.S., McGraw T.E., Friedman J.M. Insulin regulates leptin secretion from 3T3L1 adipocytes by a PI 3 kinase independent mechanism // Exp. Cell Res. 2008. Vol. 314. Р. 2249–2256.Zeigerer A., Rodeheffer M.S., McGraw T.E., Friedman J.M. Insulin regulates leptin secretion from 3T3L1 adipocytes by a PI 3 kinase independent mechanism // Exp. Cell Res. 2008. Vol. 314. Р. 2249–2256.Clapham J.C., Smith S.A., Moore G.B., Hughes M.G., Azam H., Scott A., Jung R.T. Plasma leptin concentrations and OB gene expression in subcutaneous adipose tissue are not regulated acutely by physiological hyperinsulinaemia in lean and obese humans // Int. J. Obes. Relat. Metab. Disord. 1997. Vol. 21, N 3. Р. 179–183.Clapham J.C., Smith S.A., Moore G.B., Hughes M.G., Azam H., Scott A., Jung R.T. Plasma leptin concentrations and OB gene expression in subcutaneous adipose tissue are not regulated acutely by physiological hyperinsulinaemia in lean and obese humans // Int. J. Obes. Relat. Metab. Disord. 1997. Vol. 21, N 3. Р. 179–183.Moreno-Aliaga M.J., Stanhope K.L., Havel P.J. Transcriptional regulation of the leptin promoter by insulin-stimulated glucose metabolism in 3t3-l1 adipocytes // Biochem. Biophys. Res. Commun. 2001. Vol. 283. Р. 544–548.Moreno-Aliaga M.J., Stanhope K.L., Havel P.J. Transcriptional regulation of the leptin promoter by insulin-stimulated glucose metabolism in 3t3-l1 adipocytes // Biochem. Biophys. Res. Commun. 2001. Vol. 283. Р. 544–548.Faraj M., Beauregard G., Loizon E., Moldes M., Clement K., Tahiri Y., Cianflone K., Vidal H., Rabasa-Lhoret R. Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin // J. Endocrinol. 2006. Vol. 191, N 2. Р. 427–435.Faraj M., Beauregard G., Loizon E., Moldes M., Clement K., Tahiri Y., Cianflone K., Vidal H., Rabasa-Lhoret R. Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin // J. Endocrinol. 2006. Vol. 191, N 2. Р. 427–435.Boucher J., Kleinridders A., Kahn C.R. Insulin receptor signaling in normal and insulin-resistant states // Cold Spring Harb. Perspect. Biol. 2014. Vol. 6, N 1. ID a009191.Boucher J., Kleinridders A., Kahn C.R. Insulin receptor signaling in normal and insulin-resistant states // Cold Spring Harb. Perspect. Biol. 2014. Vol. 6, N 1. ID a009191.Manning B.D., Toker A. AKT/PKB signaling: navigating the network // Cell. 2017. Vol. 169, N 3. Р. 381–405.Manning B.D., Toker A. AKT/PKB signaling: navigating the network // Cell. 2017. Vol. 169, N 3. Р. 381–405.Tsubai T., Noda Y., Ito K., Nakao M., Seino Y., Oiso Y., Hamada Y. Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose // Heliyon. 2016. Vol. 2, N 11. ID e00194 .Tsubai T., Noda Y., Ito K., Nakao M., Seino Y., Oiso Y., Hamada Y. Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose // Heliyon. 2016. Vol. 2, N 11. ID e00194 .Lee M.J., Yang R.Z., Gong D.W., Fried S.K. Feeding and insulin increase leptin translation. Importance of the leptin mRNA untranslated regions // J. Biol. Chem. 2007. Vol. 282, N 1. Р. 72–80.Lee M.J., Yang R.Z., Gong D.W., Fried S.K. Feeding and insulin increase leptin translation. Importance of the leptin mRNA untranslated regions // J. Biol. Chem. 2007. Vol. 282, N 1. Р. 72–80.Xiong Y., Xu Z., Wang Y., Kuang S., Shan T. Adipocyte-specific DKO of Lkb1 and mTOR protects mice against HFD-induced obesity, but results in insulin resistance // J. Lipid Res. 2018. Vol. 59, N 6. Р. 974–981.Xiong Y., Xu Z., Wang Y., Kuang S., Shan T. Adipocyte-specific DKO of Lkb1 and mTOR protects mice against HFD-induced obesity, but results in insulin resistance // J. Lipid Res. 2018. Vol. 59, N 6. Р. 974–981.Cong L., Chen K., Li J., Gao P., Li Q., Mi S., Wu X., Zhao A.Z. Regulation of adiponectin and leptin secretion and expression by insulin through a PI3K-PDE3B dependent mechanism in rat primary adipocytes // Biochem. J. 2007. Vol. 403, N 3. Р. 519–525.Cong L., Chen K., Li J., Gao P., Li Q., Mi S., Wu X., Zhao A.Z. Regulation of adiponectin and leptin secretion and expression by insulin through a PI3K-PDE3B dependent mechanism in rat primary adipocytes // Biochem. J. 2007. Vol. 403, N 3. Р. 519–525.Moreno-Aliaga M.J., Swarbrick M.M., Lorente-Cebrian S., Stanhope K.L., Havel P.J., Martinez J.A. Sp1-mediated transcription is involved in the induction of leptin by insulin-stimulated glucose metabolism // J. Mol. Endocrinol. 2007. Vol. 38, N 5. Р. 537–546.Moreno-Aliaga M.J., Swarbrick M.M., Lorente-Cebrian S., Stanhope K.L., Havel P.J., Martinez J.A. Sp1-mediated transcription is involved in the induction of leptin by insulin-stimulated glucose metabolism // J. Mol. Endocrinol. 2007. Vol. 38, N 5. Р. 537–546.Perez-Perez A., Maymo J., Gambino Y., Guadix P., Duenas J.L., Varone C., Sanchez-Margalet V. Insulin enhances leptin expression in human trophoblastic cells // Biol. Reprod. 2013. Vol. 89, N 1. ID 20.Perez-Perez A., Maymo J., Gambino Y., Guadix P., Duenas J.L., Varone C., Sanchez-Margalet V. Insulin enhances leptin expression in human trophoblastic cells // Biol. Reprod. 2013. Vol. 89, N 1. ID 20.Krycer J.R., Sharpe L.J., Luu W., Brown A.J. The Akt-SREBP nexus: cell signaling meets lipid metabolism // Trends Endocrinol. Metab. 2010. Vol. 21, N 5. Р. 268–276.Krycer J.R., Sharpe L.J., Luu W., Brown A.J. The Akt-SREBP nexus: cell signaling meets lipid metabolism // Trends Endocrinol. Metab. 2010. Vol. 21, N 5. Р. 268–276.McClain D.A., Lubas W.A., Cooksey R.C., Hazel M., Parker G.J., Love D.C., Hanover J.A. Altered glycandependent signaling induces insulin resistance and hyperleptinemia // Proc. Natl. Acad. Sci. U. S. A. 2002. Vol. 99, N 16. Р. 10695–10699.McClain D.A., Lubas W.A., Cooksey R.C., Hazel M., Parker G.J., Love D.C., Hanover J.A. Altered glycandependent signaling induces insulin resistance and hyperleptinemia // Proc. Natl. Acad. Sci. U. S. A. 2002. Vol. 99, N 16. Р. 10695–10699.Cammisotto P.G., Bukowiecki L.J., Deshaies Y., Bendayan M. Leptin biosynthetic pathway in white adipocytes // Biochem. Cell. Biol. 2006. Vol. 84, N 2. Р. 207–214.Cammisotto P.G., Bukowiecki L.J., Deshaies Y., Bendayan M. Leptin biosynthetic pathway in white adipocytes // Biochem. Cell. Biol. 2006. Vol. 84, N 2. Р. 207–214.Lee M.J., Wang Y., Ricci M.R., Sullivan S., Russell C.D., Fried S.K. Acute and chronic regulation of leptin synthesis, storage, and secretion by insulin and dexamethasone in human adipose tissue // Am. J. Physiol. Endocrinol. Metab. 2007. Vol. 292, N 3. Р. E858–E864.Lee M.J., Wang Y., Ricci M.R., Sullivan S., Russell C.D., Fried S.K. Acute and chronic regulation of leptin synthesis, storage, and secretion by insulin and dexamethasone in human adipose tissue // Am. J. Physiol. Endocrinol. Metab. 2007. Vol. 292, N 3. Р. E858–E864.Roh C., Thoidis G., Farmer S.R., Kandror K.V. Identification and characterization of leptin-containing intracellular compartment in rat adipose cells // Am. J. Physiol. Endocrinol. Metab. 2000. Vol. 279, N 4. Р. E893–E899.Roh C., Thoidis G., Farmer S.R., Kandror K.V. Identification and characterization of leptin-containing intracellular compartment in rat adipose cells // Am. J. Physiol. Endocrinol. Metab. 2000. Vol. 279, N 4. Р. E893–E899.Cammisotto P.G., Bukowiecki L.J. Mechanisms of leptin secretion from white adipocytes // Am. J. Physiol. Cell Physiol. 2002. Vol. 283, N 1. Р. 244–250.Cammisotto P.G., Bukowiecki L.J. Mechanisms of leptin secretion from white adipocytes // Am. J. Physiol. Cell Physiol. 2002. Vol. 283, N 1. Р. 244–250.Kolaczynski J.W., Nyce M.R, Considine R.V., Boden G., Nolan J.J., Henry R., Mudaliar S.R., Olefsky J., Caro J.F. Acute and chronic effects of insulin on leptin production in humans: studies in vivo and in vitro // Diabetes. 1996. Vol. 45, N 5. Р. 699–701.Kolaczynski J.W., Nyce M.R, Considine R.V., Boden G., Nolan J.J., Henry R., Mudaliar S.R., Olefsky J., Caro J.F. Acute and chronic effects of insulin on leptin production in humans: studies in vivo and in vitro // Diabetes. 1996. Vol. 45, N 5. Р. 699–701.Lee M.J., Fried S.K. Multilevel regulation of leptin storage, turnover, and secretion by feeding and insulin in rat adipose tissue // J. Lipid Res. 2006. Vol. 47, N 9. Р. 1984–1993.Lee M.J., Fried S.K. Multilevel regulation of leptin storage, turnover, and secretion by feeding and insulin in rat adipose tissue // J. Lipid Res. 2006. Vol. 47, N 9. Р. 1984–1993.Russell C.D., Ricci M.R., Brolin R.E., Magill E., Fried S.K. Regulation of the leptin content of obese human adipose tissue // Am. J. Physiol. Endocrinol. Metab. 2001. Vol. 280, N 3. Р. E399–E404.Russell C.D., Ricci M.R., Brolin R.E., Magill E., Fried S.K. Regulation of the leptin content of obese human adipose tissue // Am. J. Physiol. Endocrinol. Metab. 2001. Vol. 280, N 3. Р. E399–E404.Wang Y., Ali Y., Lim C.Y., Hong W., Pang Z.P., Han W. Insulin-stimulated leptin secretion requires calcium and PI3K/Akt activation // Biochem. J. 2014. Vol. 458, N 3. Р. 491–498.Wang Y., Ali Y., Lim C.Y., Hong W., Pang Z.P., Han W. Insulin-stimulated leptin secretion requires calcium and PI3K/Akt activation // Biochem. J. 2014. Vol. 458, N 3. Р. 491–498.Груздева О.В., Акбашева О.Е., Дылева Ю.А., Антонова Л.В., Матвеева В.Г., Учасова Е.Г., Фанаскова Е.В., Каретникова В.Н., Иванов С.В., Барбараш О.Л. Адипокиновый и цитокиновый профили эпикардиальной и подкожной жировой ткани у пациентов с ишемической болезнью сердца // Бюл. эксперим. биологии и медицины. 2017. Т. 163, N 5. С. 560–563.Груздева О.В., Акбашева О.Е., Дылева Ю.А., Антонова Л.В., Матвеева В.Г., Учасова Е.Г., Фанаскова Е.В., Каретникова В.Н., Иванов С.В., Барбараш О.Л. Адипокиновый и цитокиновый профили эпикардиальной и подкожной жировой ткани у пациентов с ишемической болезнью сердца // Бюл. эксперим. биологии и медицины. 2017. Т. 163, N 5. С. 560–563.Gruzdeva O., Uchasova E., Dyleva Y., Borodkina D., Akbasheva O., Belik E., Karetnikova V., Brel N., Kokov A., Kashtalap V., Barbarash O. Relationships between epicardial adipose tissue thickness and adipo-fibrokine indicator profiles post-myocardial infarction // Cardiovasc. Diabetol. 2018. Vol. 17. ID 40.Gruzdeva O., Uchasova E., Dyleva Y., Borodkina D., Akbasheva O., Belik E., Karetnikova V., Brel N., Kokov A., Kashtalap V., Barbarash O. Relationships between epicardial adipose tissue thickness and adipo-fibrokine indicator profiles post-myocardial infarction // Cardiovasc. Diabetol. 2018. Vol. 17. ID 40.Zeigerer A., Rodeheffer M.S., McGraw T.E., Friedman J.M. Insulin regulates leptin secretion from 3T3L1 adipocytes by a PI 3 kinase independent mechanism // Exp. Cell Res. 2008. Vol. 314, N 11-12. Р. 2249–2256.Zeigerer A., Rodeheffer M.S., McGraw T.E., Friedman J.M. Insulin regulates leptin secretion from 3T3L1 adipocytes by a PI 3 kinase independent mechanism // Exp. Cell Res. 2008. Vol. 314, N 11-12. Р. 2249–2256.Minokoshi Y., Kim Y.B., Peroni O.D., Fryer L.G., Muller C., Carling D., Kahn B.B. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase // Nature. 2002. Vol. 415, N 6869. Р. 339–343.Minokoshi Y., Kim Y.B., Peroni O.D., Fryer L.G., Muller C., Carling D., Kahn B.B. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase // Nature. 2002. Vol. 415, N 6869. Р. 339–343.Lago F., Dieguez C., Gуmez-Reino J., Gualillo O. Adipokines as emerging mediators of immune response and inflammation // Nat. Clin. Pract. Rheumatol. 2007. Vol. 3. Р. 716–724.Lago F., Dieguez C., Gуmez-Reino J., Gualillo O. Adipokines as emerging mediators of immune response and inflammation // Nat. Clin. Pract. Rheumatol. 2007. Vol. 3. Р. 716–724.

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