ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet13040ometendo-13040Research ArticleОБЗОРЫREVIEWSМетаболические эффекты альдостеронаMetabolic effects of aldosteronehttps://orcid.org/0000-0002-0786-7809ИващенкоК. В.IvashchenkoK. V.

Иващенко Ксения Валерьевна

117036, Москва, ул. Дм. Ульянова, д. 11

Kseniya V. Ivashchenko – MD.

11 Dm. Ulyanova street, 117036 Moscow

kseniya223@mail.ruhttps://orcid.org/0000-0001-8077-9381МазуринаН. В.MazurinaN. V.

Мазурина Наталия Валентиновна - д.м.н.

Москва

Natalya V. Mazurina - MD, PhD.

Moscow

natalyamazurina@mail.ruhttps://orcid.org/0000-0001-6388-1544ПлатоноваН. М.PlatonovaN. M.

Платонова Надежда Михайловна - д.м.н.

Москва

Nadegda M. Platonova - MD, PhD.

Moscow

doc-platonova@inbox.ruhttps://orcid.org/0000-0002-8520-8702ТрошинаЕ. А.TroshinaE. A.

Трошина Екатерина Анатольевна - д.м.н., профессор.

Москва

Ekaterina A. Troshina - MD, PhD, Professor.

Moscow

troshina@inbox.ruНациональный медицинский исследовательский центр эндокринологииРоссияEndocrinology Research CentreRussian Federation202322012024204291300Copyright © Иващенко К.В., Мазурина Н.В., Платонова Н.М., Трошина Е.А., 20242024Иващенко К.В., Мазурина Н.В., Платонова Н.М., Трошина Е.А.Ivashchenko K.V., Mazurina N.V., Platonova N.M., Troshina E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/13040

К настоящему моменту накоплены факты, свидетельствующие о взаимном влиянии альдостерона и жировой ткани. Доказаны как повышение уровня альдостерона у пациентов с ожирением и метаболическим синдромом, так и прямое влияние альдостерона на жировую ткань путем активации анаболических процессов и повышения экспрессии минералокортикоидных рецепторов (МКР). В свою очередь, избыточная активация МКР приводит к стимуляции адипогенеза и увеличению объема жировой ткани. Избыток альдостерона может рассматриваться в качестве самостоятельного фактора сердечно-сосудистого риска, оказывающего влияние на такие процессы, как фиброз миокарда, нефросклероз, атеросклероз. Существуют убедительные данные об увеличении частоты и более тяжелом течении нарушений углеводного и липидного обмена у пациентов с первичным гиперальдостеронизмом. Формирование сходных патологических изменений также наблюдается у пациентов с ожирением и метаболическим синдромом. В данном обзоре представлены научные данные о метаболических эффектах альдостерона, в частности, о влиянии, которое он оказывает на функцию жировой ткани, углеводный и липидный обмен. Терапия антагонистами МКР может оказывать положительное влияние на течение метаболического синдрома, способствовать стабилизации углеводного и липидного обмена, улучшать клинический статус пациентов с сердечно-сосудистыми заболеваниями и снижать риски развития осложнений. Однако уровень доказательности проведенных исследований не является достаточным, чтобы обосновать внедрение такой терапии в клиническую практику.

Currently, increasing evidence shows the mutual influence of aldosterone and adipose tissue. Aldosterone excess has been reported in patients with obesity and metabolic syndrome. Aldosterone has a direct effect on adipose tissue increasing anabolic activity and expression of mineralocorticoid receptors. In turn, excessive activation of MCR leads to stimulation of adipogenesis and an increase in the volume of adipose tissue. Aldosterone excess can be considered an independent cardiovascular risk factor that affects such processes as cardiac fibrosis, nephrosclerosis, and arteriosclerosis. There is convincing evidence of higher prevalence and severity of impaired glucose homeostasis and lipid metabolism disorders among patients with primary hyperaldosteronism. Similar pathological changes are also observed in patients with obesity and metabolic syndrome. This review presents scientific data on the metabolic effects of aldosterone, in particular its effect on adipose tissue function, glucose and lipid metabolism. Treatment with mineralocorticoid receptor antagonists may provide substantial benefit in the management of metabolic syndrome, contribute to the stabilisation of glucose and lipid metabolism, improve clinical status of patients with cardiovascular diseases and reduce the risk of complications. However, available evidence from the conducted studies is not sufficient to justify introduction of such therapy into clinical practice.

альдостероножирениеметаболический синдромпервичный гиперальдостеронизмуглеводный обменжировая тканьренин-ангиотензин-альдостероновая системаaldosteroneobesitymetabolic syndromeprimary hyperaldosteronismglucose homeostasisfat tissuerenin-angiotensin-aldosterone systemРабота выполнена в рамках государственного задания Минздрава России «Разработка новых технологий диагностики и мониторинга опухолей коры надпочечников с использованием метаболомных и протеомных технологий», рег. № 123021300098-7ReferencesFunder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi: https://doi.org/10.1210/jc.2015-4061Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi: https://doi.org/10.1210/jc.2015-4061Cohn JN, Colucci W. Cardiovascular effects of aldosterone and post–acute myocardial infarction pathophysiology. Am J Cardiol. 2006;97(10):4-12. doi: https://doi.org/10.1016/j.amjcard.2006.03.004Cohn JN, Colucci W. Cardiovascular effects of aldosterone and post–acute myocardial infarction pathophysiology. Am J Cardiol. 2006;97(10):4-12. doi: https://doi.org/10.1016/j.amjcard.2006.03.004Schiffrin EL. Effects of aldosterone on the vasculature. Hypertension. 2006;47(3):312-318. doi: https://doi.org/10.1161/01.HYP.0000201443.63240.a7Schiffrin EL. Effects of aldosterone on the vasculature. Hypertension. 2006;47(3):312-318. doi: https://doi.org/10.1161/01.HYP.0000201443.63240.a7Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi: https://doi.org/10.1210/jc.2015-4061Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi: https://doi.org/10.1210/jc.2015-4061Cohn JN, Colucci W. Cardiovascular Effects of Aldosterone and Post–Acute Myocardial Infarction Pathophysiology. Am J Cardiol. 2006;97(10):4-12. doi: https://doi.org/10.1016/j.amjcard.2006.03.004Cohn JN, Colucci W. Cardiovascular Effects of Aldosterone and Post–Acute Myocardial Infarction Pathophysiology. Am J Cardiol. 2006;97(10):4-12. doi: https://doi.org/10.1016/j.amjcard.2006.03.004Schiffrin EL. Effects of aldosterone on the vasculature. Hypertension. 2006;47(3):312-318. doi: https://doi.org/10.1161/01.HYP.0000201443.63240.a7Schiffrin EL. Effects of aldosterone on the vasculature. Hypertension. 2006;47(3):312-318. doi: https://doi.org/10.1161/01.HYP.0000201443.63240.a7Malik S, Wong ND, Franklin SS, et al. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation. 2004;110(10):1245-1250. doi: https://doi.org/10.1161/01.CIR.0000140677.20606.0EMalik S, Wong ND, Franklin SS, et al. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation. 2004;110(10):1245-1250. doi: https://doi.org/10.1161/01.CIR.0000140677.20606.0EWolf G. After all those fat years: renal consequences of obesity. Nephrol Dial Transplant. 2003;18(12):2471-2474. doi: https://doi.org/10.1093/ndt/gfg427Wolf G. After all those fat years: renal consequences of obesity. Nephrol Dial Transplant. 2003;18(12):2471-2474. doi: https://doi.org/10.1093/ndt/gfg427Calhoun DA. Is there an unrecognized epidemic of primary aldosteronism? (Pro). Hypertension. 2007;50(3):447-453. doi: https://doi.org/10.1161/HYPERTENSIONAHA.106.086116Calhoun DA. Is there an unrecognized epidemic of primary aldosteronism? (Pro). Hypertension. 2007;50(3):447-453. doi: https://doi.org/10.1161/HYPERTENSIONAHA.106.086116Kaplan NM. Is there an unrecognized epidemic of primary aldosteronism? (Con). Hypertension. 2007;50(3):454-458. doi: https://doi.org/10.1161/HYPERTENSIONAHA.106.086124Kaplan NM. Is there an unrecognized epidemic of primary aldosteronism? (Con). Hypertension. 2007;50(3):454-458. doi: https://doi.org/10.1161/HYPERTENSIONAHA.106.086124Мельниченко Г.А., Платонова Н.М., Бельцевич Д.Г., и др. Первичный гиперальдостеронизм: диагностика и лечение. Новый взгляд на проблему. По материалам Проекта клинических рекомендаций Российской ассоциации эндокринологов по диагностике и лечению первичного гиперальдостеронизма. // ConsiliumMedicum. — 2017. — Т. 19. — №4. — С. 75-85. doi: https://doi.org/10.26442/2075-1753_19.4.75-85Melnichenko GA, Platonova NM, Beltsevich DG, et al. Primary hyperaldosteronism: diagnosis and treatment. a new look at the problem. according to the materials of the russian association of endocrinologists clinical guidelines for primary hyperaldosteronism diagnosis and treatment. Consilium Medicum. 2017;19(4):75-85. (In Russ.). doi: https://doi.org/10.26442/2075-1753_19.4.75-85Milliez P, Girerd X, Plouin P-F, et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005;45(8):1243-1248. doi: https://doi.org/10.1016/j.jacc.2005.01.015Milliez P, Girerd X, Plouin P-F, et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005;45(8):1243-1248. doi: https://doi.org/10.1016/j.jacc.2005.01.015Rossi GP, Bernini G, Desideri G, et al. Renal damage in primary aldosteronism. Hypertension. 2006;48(2):232-238. doi: https://doi.org/10.1161/01.HYP.0000230444.01215.6aRossi GP, Bernini G, Desideri G, et al. Renal damage in primary aldosteronism. Hypertension. 2006;48(2):232-238. doi: https://doi.org/10.1161/01.HYP.0000230444.01215.6aBender SB, McGraw AP, Jaffe IZ, Sowers JR. Mineralocorticoid receptor–mediated vascular insulin resistance. Diabetes. 2013;62(2):313-319. doi: https://doi.org/10.2337/db12-0905Bender SB, McGraw AP, Jaffe IZ, Sowers JR. Mineralocorticoid receptor–mediated vascular insulin resistance. Diabetes. 2013;62(2):313-319. doi: https://doi.org/10.2337/db12-0905Hawkins UA, Gomez-Sanchez EP, Gomez-Sanchez CM, Gomez-Sanchez CE. The ubiquitous mineralocorticoid receptor: Clinical implications. Curr Hypertens Rep. 2012;14(6):573-580. doi: https://doi.org/10.1007/s11906-012-0297-0Hawkins UA, Gomez-Sanchez EP, Gomez-Sanchez CM, GomezSanchez CE. The ubiquitous mineralocorticoid receptor: Clinical implications. Curr Hypertens Rep. 2012;14(6):573-580. doi: https://doi.org/10.1007/s11906-012-0297-0Kobayashi N, Yoshida K, Nakano S, et al. Cardioprotective mechanisms of eplerenone on cardiac performance and remodeling in failing rat hearts. Hypertension. 2006;47(4):671-679. doi: https://doi.org/10.1161/01.HYP.0000203148.42892.7aKobayashi N, Yoshida K, Nakano S, et al. Cardioprotective mechanisms of eplerenone on cardiac performance and remodeling in failing rat hearts. Hypertension. 2006;47(4):671-679. doi: https://doi.org/10.1161/01.HYP.0000203148.42892.7aNagata K, Obata K, Xu J, et al. Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and failure in lowaldosterone hypertensive rats. Hypertension. 2006;47(4):656-664. doi: https://doi.org/10.1161/01.HYP.0000203772.78696.67Nagata K, Obata K, Xu J, et al. Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and failure in lowaldosterone hypertensive rats. Hypertension. 2006;47(4):656-664. doi: https://doi.org/10.1161/01.HYP.0000203772.78696.67Fallo F, Veglio F, Bertello C, et al. Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J Clin Endocrinol Metab. 2006;91(2):454-459. doi: https://doi.org/10.1210/jc.2005-1733Fallo F, Veglio F, Bertello C, et al. Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J Clin Endocrinol Metab. 2006;91(2):454-459. doi: https://doi.org/10.1210/jc.2005-1733Matrozova J, Steichen O, Amar L, et al. Fasting plasma glucose and serum lipids in patients with primary aldosteronism. Hypertension. 2009;53(4):605-610. doi: https://doi.org/10.1161/HYPERTENSIONAHA.108.122002Matrozova J, Steichen O, Amar L, et al. Fasting plasma glucose and serum lipids in patients with primary aldosteronism. Hypertension. 2009;53(4):605-610. doi: https://doi.org/10.1161/HYPERTENSIONAHA.108.122002Monticone S, D’Ascenzo F, Moretti C, et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018;6(1):41-50. doi: https://doi.org/10.1016/S2213-8587(17)30319-4Monticone S, D’Ascenzo F, Moretti C, et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018;6(1):41-50. doi: https://doi.org/10.1016/S2213-8587(17)30319-4Mosso LM, Carvajal CA, Maiz A, et al. A possible association between primary aldosteronism and a lower beta-cell function. Journal of hypertension. 2007;25(10):2125-2130. doi:10.1097/HJH.0b013e3282861fa4Mosso LM, Carvajal CA, Maiz A, et al. A possible association between primary aldosteronism and a lower beta-cell function. Journal of hypertension. 2007;25(10):2125-2130. doi:10.1097/HJH.0b013e3282861fa4Hanslik G, Wallaschofski H, Dietz A, et al. Increased prevalence of diabetes mellitus and the metabolic syndrome in patients with primary aldosteronism of the German Conn’s Registry. Eur J Endocrinol. 2015;173(5):665-675. doi: https://doi.org/10.1530/EJE-15-0450Hanslik G, Wallaschofski H, Dietz A, et al. Increased prevalence of diabetes mellitus and the metabolic syndrome in patients with primary aldosteronism of the German Conn’s Registry. Eur J Endocrinol. 2015;173(5):665-675. doi: https://doi.org/10.1530/EJE-15-0450Turchi F, Ronconi V, di Tizio V, et al. Primary aldosteronism and essential hypertension: Assessment of cardiovascular risk at diagnosis and after treatment. Nutr Metab Cardiovasc Dis. 2014;24(5):476-482. doi: https://doi.org/10.1016/j.numecd.2013.09.009Turchi F, Ronconi V, di Tizio V, et al. Primary aldosteronism and essential hypertension: Assessment of cardiovascular risk at diagnosis and after treatment. Nutr Metab Cardiovasc Dis. 2014;24(5):476-482. doi: https://doi.org/10.1016/j.numecd.2013.09.009Wu V-C, Chueh S-CJ, Chen L, et al. Risk of new-onset diabetes mellitus in primary aldosteronism. J Hypertens. 2017;35(8):1698-1708. doi: https://doi.org/10.1097/HJH.0000000000001361Wu V-C, Chueh S-CJ, Chen L, et al. Risk of new-onset diabetes mellitus in primary aldosteronism. J Hypertens. 2017;35(8):1698-1708. doi: https://doi.org/10.1097/HJH.0000000000001361Adler GK, Murray GR, Turcu AF, et al. Primary aldosteronism decreases insulin secretion and increases insulin clearance in humans. Hypertension. 2020;75(5):1251-1259. doi: https://doi.org/10.1161/HYPERTENSIONAHA.119.13922Adler GK, Murray GR, Turcu AF, et al. Primary aldosteronism decreases insulin secretion and increases insulin clearance in humans. Hypertension. 2020;75(5):1251-1259. doi: https://doi.org/10.1161/HYPERTENSIONAHA.119.13922Fischer E, Adolf C, Pallauf A, et al. Aldosterone excess impairs first phase insulin secretion in primary aldosteronism. J Clin Endocrinol Metab. 2013;98(6):2513-2520. doi: https://doi.org/10.1210/jc.2012-3934Fischer E, Adolf C, Pallauf A, et al. Aldosterone excess impairs first phase insulin secretion in primary aldosteronism. J Clin Endocrinol Metab. 2013;98(6):2513-2520. doi: https://doi.org/10.1210/jc.2012-3934Komada H, Hirota Y, So A, et al. Insulin secretion and sensitivity before and after surgical treatment for aldosteroneproducing adenoma. Diabetes Metab. 2020;46(3):236-242. doi: https://doi.org/10.1016/j.diabet.2019.10.002Komada H, Hirota Y, So A, et al. Insulin secretion and sensitivity before and after surgical treatment for aldosteroneproducing adenoma. Diabetes Metab. 2020;46(3):236-242. doi: https://doi.org/10.1016/j.diabet.2019.10.002Jin HM, Zhou DC, Gu HF, et al. Antioxidant N-acetylcysteine protects pancreatic β-cells against aldosterone-induced oxidative stress and apoptosis in female db/db Mice and Insulin-Producing MIN6 cells. Endocrinology. 2013;154(11):4068-4077. doi: https://doi.org/10.1210/en.2013-1115Jin HM, Zhou DC, Gu HF, et al. Antioxidant N-acetylcysteine protects pancreatic β-cells against aldosterone-induced oxidative stress and apoptosis in female db/db Mice and InsulinProducing MIN6 cells. Endocrinology. 2013;154(11):4068-4077. doi: https://doi.org/10.1210/en.2013-1115Luther JM, Luo P, Kreger MT, et al. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets. Diabetologia. 2011;54(8):2152-2163. doi: https://doi.org/10.1007/s00125-011-2158-9Luther JM, Luo P, Kreger MT, et al. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets. Diabetologia. 2011;54(8):2152-2163. doi: https://doi.org/10.1007/s00125-011-2158-9Chen F, Liu J, Wang Y, et al. Aldosterone induces clonal β-cell failure through glucocorticoid receptor. Sci Rep. 2015;5(1):13215. doi: https://doi.org/10.1038/srep13215Chen F, Liu J, Wang Y, et al. Aldosterone induces clonal β-cell failure through glucocorticoid receptor. Sci Rep. 2015;5(1):13215. doi: https://doi.org/10.1038/srep13215Shibayama Y, Wada N, Baba S, et al. Relationship between visceral fat and plasma aldosterone concentration in patients with primary aldosteronism. J Endocr Soc. 2018;2(11):1236-1245. doi: https://doi.org/10.1210/js.2018-00187Shibayama Y, Wada N, Baba S, et al. Relationship between visceral fat and plasma aldosterone concentration in patients with primary aldosteronism. J Endocr Soc. 2018;2(11):1236-1245. doi: https://doi.org/10.1210/js.2018-00187Chen K-M, Lee B-C, Chen P-T, et al. Evaluation of abdominal computed tomography scans for differentiating the discrepancies in abdominal adipose tissue between two major subtypes of primary aldosteronism. Front Endocrinol (Lausanne). 2021;(12):647184. doi: https://doi.org/10.3389/fendo.2021.647184Chen K-M, Lee B-C, Chen P-T, et al. Evaluation of abdominal computed tomography scans for differentiating the discrepancies in abdominal adipose tissue between two major subtypes of primary aldosteronism. Front Endocrinol (Lausanne). 2021;(12):647184. doi: https://doi.org/10.3389/fendo.2021.647184Ohno Y, Sone M, Inagaki N, et al. Obesity as a key factor underlying idiopathic hyperaldosteronism. J Clin Endocrinol Metab. 2018;103(12):4456-4464. doi: https://doi.org/10.1210/jc.2018-00866Ohno Y, Sone M, Inagaki N, et al. Obesity as a key factor underlying idiopathic hyperaldosteronism. J Clin Endocrinol Metab. 2018;103(12):4456-4464. doi: https://doi.org/10.1210/jc.2018-00866Hirata A, Maeda N, Nakatsuji H, et al. Contribution of glucocorticoid–mineralocorticoid receptor pathway on the obesity-related adipocyte dysfunction. Biochem Biophys Res Commun. 2012;419(2):182-187. doi: https://doi.org/10.1016/j.bbrc.2012.01.139Hirata A, Maeda N, Nakatsuji H, et al. Contribution of glucocorticoid– mineralocorticoid receptor pathway on the obesity-related adipocyte dysfunction. Biochem Biophys Res Commun. 2012;419(2):182-187. doi: https://doi.org/10.1016/j.bbrc.2012.01.139Thuzar M, Stowasser M. The mineralocorticoid receptor— an emerging player in metabolic syndrome? J Hum Hypertens. 2021;35(2):117-123. doi: https://doi.org/10.1038/s41371-020-00467-3Thuzar M, Stowasser M. The mineralocorticoid receptor— an emerging player in metabolic syndrome? J Hum Hypertens. 2021;35(2):117-123. doi: https://doi.org/10.1038/s41371-020-00467-3Edwards CRW, Burt D, Mcintyre MA, et al. Localisation of 11β-hydroxysteroid dehydrogenase—tissue specific protector of the mineralocorticoid receptor. Lancet. 1988;332(8618):986-989. doi: https://doi.org/10.1016/S0140-6736(88)90742-8Edwards CRW, Burt D, Mcintyre MA, et al. Localisation of 11β-hydroxysteroid dehydrogenase—tissue specific protector of the mineralocorticoid receptor. Lancet. 1988;332(8618):986-989. doi: https://doi.org/10.1016/S0140-6736(88)90742-8Funder JW, Pearce PT, Smith R, Smith AI. Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science (80-). 1988;242(4878):583-585. doi: https://doi.org/10.1126/science.2845584Funder JW, Pearce PT, Smith R, Smith AI. Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science (80-). 1988;242(4878):583-585. doi: https://doi.org/10.1126/science.2845584Urbanet R, Nguyen Dinh Cat A, Feraco A, et al. Adipocyte mineralocorticoid receptor activation leads to metabolic syndrome and induction of prostaglandin D2 synthase. Hypertension. 2015;66(1):149-157. doi: https://doi.org/10.1161/HYPERTENSIONAHA.114.04981Urbanet R, Nguyen Dinh Cat A, Feraco A, et al. Adipocyte mineralocorticoid receptor activation leads to metabolic syndrome and induction of prostaglandin D2 synthase. Hypertension. 2015;66(1):149-157. doi: https://doi.org/10.1161/HYPERTENSIONAHA.114.04981Tuck ML, Sowers J, Dornfeld L, et al. The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients. N Engl J Med. 1981;304(16):930-933. doi: https://doi.org/10.1056/NEJM198104163041602Tuck ML, Sowers J, Dornfeld L, et al. The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients. N Engl J Med. 1981;304(16):930-933. doi: https://doi.org/10.1056/NEJM198104163041602Thatcher S, Yiannikouris F, Gupte M, Cassis L. The adipose renin–angiotensin system: Role in cardiovascular disease. Mol Cell Endocrinol. 2009;302(2):111-117. doi: https://doi.org/10.1016/j.mce.2009.01.019Thatcher S, Yiannikouris F, Gupte M, Cassis L. The adipose renin– angiotensin system: Role in cardiovascular disease. Mol Cell Endocrinol. 2009;302(2):111-117. doi: https://doi.org/10.1016/j.mce.2009.01.019Boschmann M, Ringel J, Klaus S, Sharma AM. Metabolic and hemodynamic response of adipose tissue to angiotensin II. Obes Res. 2001;9(8):486-491. doi: https://doi.org/10.1038/oby.2001.63Boschmann M, Ringel J, Klaus S, Sharma AM. Metabolic and hemodynamic response of adipose tissue to angiotensin II. Obes Res. 2001;9(8):486-491. doi: https://doi.org/10.1038/oby.2001.63Дедов И.И., Мельниченко Г.А., Бутрова С.А. Жировая ткань как эндокринный орган // Ожирение и метаболизм. — 2006. — Т. 3. — №1. — С. 6-13.Dedov II, Mel’nichenko GA, Butrova SA. Zhirovaya tkan’ kak endokrinnyy organ. Obesity and metabolism. 2006;3(1):6-13. (In Russ.). doi: https://doi.org/10.14341/2071-8713-4937Bentley-Lewis R, Adler GK, Perlstein T, et al. Body mass index predicts aldosterone production in normotensive adults on a high-salt diet. J Clin Endocrinol Metab. 2007;92(11):4472-4475. doi: https://doi.org/10.1210/jc.2007-1088Bentley-Lewis R, Adler GK, Perlstein T, et al. Body mass index predicts aldosterone production in normotensive adults on a high-salt diet. J Clin Endocrinol Metab. 2007;92(11):4472-4475. doi: https://doi.org/10.1210/jc.2007-1088Ho J, Keogh J, Bornstein S, et al. Moderate weight loss reduces renin and aldosterone but does not influence basal or stimulated pituitary-adrenal axis function. Horm Metab Res. 2007;39(9):694-699. doi: https://doi.org/10.1055/s-2007-985354Ho J, Keogh J, Bornstein S, et al. Moderate weight loss reduces renin and aldosterone but does not influence basal or stimulated pituitary-adrenal axis function. Horm Metab Res. 2007;39(9):694-699. doi: https://doi.org/10.1055/s-2007-985354Engeli S, Böhnke J, Gorzelniak K, et al. Weight loss and the renin-angiotensin-aldosterone system. Hypertension. 2005;45(3):356-362. doi: https://doi.org/10.1161/01.HYP.0000154361.47683.d3Engeli S, Böhnke J, Gorzelniak K, et al. Weight loss and the reninangiotensin-aldosterone system. Hypertension. 2005;45(3):356-362. doi: https://doi.org/10.1161/01.HYP.0000154361.47683.d3Petrasek D, Jensen G, Tuck M, Stern N. effects of insulin on aldosterone production in rat zona glomerulosa cells. Life Sci. 1992;50(23):1781-1787. doi: https://doi.org/10.1016/0024-3205(92)90062-TPetrasek D, Jensen G, Tuck M, Stern N. effects of insulin on aldosterone production in rat zona glomerulosa cells. Life Sci. 1992;50(23):1781-1787. doi: https://doi.org/10.1016/0024-3205(92)90062-TGoodfriend TL, Egan B, Stepniakowski K, Ball DL. Relationships among plasma aldosterone, high-density lipoprotein cholesterol, and insulin in humans. Hypertension. 1995;25(1):30-36. doi: https://doi.org/10.1161/01.HYP.25.1.30Goodfriend TL, Egan B, Stepniakowski K, Ball DL. Relationships among plasma aldosterone, high-density lipoprotein cholesterol, and insulin in humans. Hypertension. 1995;25(1):30-36. doi: https://doi.org/10.1161/01.HYP.25.1.30Colussi G, Catena C, Lapenna R, et al. Insulin resistance and hyperinsulinemia are related to plasma aldosterone levels in hypertensive patients. Diabetes Care. 2007;30(9):2349-2354. doi: https://doi.org/10.2337/dc07-0525Colussi G, Catena C, Lapenna R, et al. Insulin resistance and hyperinsulinemia are related to plasma aldosterone levels in hypertensive patients. Diabetes Care. 2007;30(9):2349-2354. doi: https://doi.org/10.2337/dc07-0525Goodfriend TL, Ball DL, Egan BM, et al. Epoxy-Keto Derivative of Linoleic Acid Stimulates Aldosterone Secretion. Hypertension. 2004;43(2):358-363. doi: https://doi.org/10.1161/01.HYP.0000113294.06704.64Goodfriend TL, Ball DL, Egan BM, et al. Epoxy-Keto Derivative of Linoleic Acid Stimulates Aldosterone Secretion. Hypertension. 2004;43(2):358-363. doi: https://doi.org/10.1161/01.HYP.0000113294.06704.64Kidambi S, Kotchen JM, Grim CE, et al. Association of adrenal steroids with hypertension and the metabolic syndrome in blacks. Hypertension. 2007;49(3):704-711. doi: https://doi.org/10.1161/01.HYP.0000253258.36141.c7Kidambi S, Kotchen JM, Grim CE, et al. Association of adrenal steroids with hypertension and the metabolic syndrome in blacks. Hypertension. 2007;49(3):704-711. doi: https://doi.org/10.1161/01.HYP.0000253258.36141.c7Bochud M, Nussberger J, Bovet P, et al. Plasma aldosterone is independently associated with the metabolic syndrome. Hypertension. 2006;48(2):239-245. doi: https://doi.org/10.1161/01.HYP.0000231338.41548.fcBochud M, Nussberger J, Bovet P, et al. Plasma aldosterone is independently associated with the metabolic syndrome. Hypertension. 2006;48(2):239-245. doi: https://doi.org/10.1161/01.HYP.0000231338.41548.fcSchinner S, Willenberg HS, Krause D, et al. Adipocyte-derived products induce the transcription of the StAR promoter and stimulate aldosterone and cortisol secretion from adrenocortical cells through the Wnt-signaling pathway. Int J Obes. 2007;31(5):864-870. doi: https://doi.org/10.1038/sj.ijo.0803508Schinner S, Willenberg HS, Krause D, et al. Adipocyte-derived products induce the transcription of the StAR promoter and stimulate aldosterone and cortisol secretion from adrenocortical cells through the Wnt-signaling pathway. Int J Obes. 2007;31(5):864-870. doi: https://doi.org/10.1038/sj.ijo.0803508Cheng L, Wang J, Dai H, et al. Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus. Adipocyte. 2021;10(1):48-65. doi: https://doi.org/10.1080/21623945.2020.1870060Cheng L, Wang J, Dai H, et al. Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus. Adipocyte. 2021;10(1):48-65. doi: https://doi.org/10.1080/21623945.2020.1870060Chondronikola M, Volpi E, Børsheim E, et al. Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans. Diabetes. 2014;63(12):4089-4099. doi: https://doi.org/10.2337/db14-0746Chondronikola M, Volpi E, Børsheim E, et al. Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans. Diabetes. 2014;63(12):4089-4099. doi: https://doi.org/10.2337/db14-0746Kraus D, Jäger J, Meier B, et al. Aldosterone inhibits uncoupling protein-1, induces insulin resistance, and stimulates proinflammatory adipokines in adipocytes. Horm Metab Res. 2005;37(7):455-459. doi: https://doi.org/10.1055/s-2005-870240Kraus D, Jäger J, Meier B, et al. Aldosterone inhibits uncoupling protein-1, induces insulin resistance, and stimulates proinflammatory adipokines in adipocytes. Horm Metab Res. 2005;37(7):455-459. doi: https://doi.org/10.1055/s-2005-870240Viengchareun S, Penfornis P, Zennaro M-C, Lombès M. Mineralocorticoid and glucocorticoid receptors inhibit UCP expression and function in brown adipocytes. Am J Physiol Metab. 2001;280(4):E640-E649. doi: https://doi.org/10.1152/ajpendo.2001.280.4.E640Viengchareun S, Penfornis P, Zennaro M-C, Lombès M. Mineralocorticoid and glucocorticoid receptors inhibit UCP expression and function in brown adipocytes. Am J Physiol Metab. 2001;280(4):E640-E649. doi: https://doi.org/10.1152/ajpendo.2001.280.4.E640Armani A, Cinti F, Marzolla V, et al. Mineralocorticoid receptor antagonism induces browning of white adipose tissue through impairment of autophagy and prevents adipocyte dysfunction in high‐fat‐diet‐fed mice. FASEB J. 2014;28(8):3745-3757. doi: https://doi.org/10.1096/fj.13-245415Armani A, Cinti F, Marzolla V, et al. Mineralocorticoid receptor antagonism induces browning of white adipose tissue through impairment of autophagy and prevents adipocyte dysfunction in high‐fat‐diet‐fed mice. FASEB J. 2014;28(8):3745-3757. doi: https://doi.org/10.1096/fj.13-245415McNeill BT, Suchacki KJ, Stimson RH. Mechanisms in endocrinology: Human brown adipose tissue as a therapeutic target: warming up or cooling down? Eur J Endocrinol. 2021;184(6):R243-R259. doi: https://doi.org/10.1530/EJE-20-1439McNeill BT, Suchacki KJ, Stimson RH. Mechanisms in endocrinology: Human brown adipose tissue as a therapeutic target: warming up or cooling down? Eur J Endocrinol. 2021;184(6):R243-R259. doi: https://doi.org/10.1530/EJE-20-1439Thuzar M, Law WP, Dimeski G, et al. Mineralocorticoid antagonism enhances brown adipose tissue function in humans: A randomized placebo‐controlled crossover study. Diabetes, Obes Metab. 2019;21(3):509-516. doi: https://doi.org/10.1111/dom.13539Thuzar M, Law WP, Dimeski G, et al. Mineralocorticoid antagonism enhances brown adipose tissue function in humans: A randomized placebo‐controlled crossover study. Diabetes, Obes Metab. 2019;21(3):509-516. doi: https://doi.org/10.1111/dom.13539Rondinone CM, Rodbard D, Baker ME. Aldosterone stimulated differentiation of mouse 3T3-L1 cells into adipocytes. Endocrinology. 1993;132(6):2421-2426. doi: https://doi.org/10.1210/endo.132.6.8504747Rondinone CM, Rodbard D, Baker ME. Aldosterone stimulated differentiation of mouse 3T3-L1 cells into adipocytes. Endocrinology. 1993;132(6):2421-2426. doi: https://doi.org/10.1210/endo.132.6.8504747Hoppmann J, Perwitz N, Meier B, et al. The balance between gluco- and mineralo-corticoid action critically determines inflammatory adipocyte responses. J Endocrinol. 2010;204(2):153-164. doi: https://doi.org/10.1677/JOE-09-0292Hoppmann J, Perwitz N, Meier B, et al. The balance between gluco- and mineralo-corticoid action critically determines inflammatory adipocyte responses. J Endocrinol. 2010;204(2):153-164. doi: https://doi.org/10.1677/JOE-09-0292Parasiliti-Caprino M, Bollati M, et al. Adipose tissue dysfunction in obesity: Role of mineralocorticoid receptor. Nutrients. 2022;14(22):4735. doi: https://doi.org/10.3390/nu14224735Parasiliti-Caprino M, Bollati M, et al. Adipose tissue dysfunction in obesity: Role of mineralocorticoid receptor. Nutrients. 2022;14(22):4735. doi: https://doi.org/10.3390/nu14224735Guo C, Ricchiuti V, Lian BQ, et al. Mineralocorticoid Receptor Blockade Reverses Obesity-Related Changes in Expression of Adiponectin, Peroxisome Proliferator-Activated Receptor-γ, and Proinflammatory Adipokines. Circulation. 2008;117(17):2253-2261. doi: https://doi.org/10.1161/CIRCULATIONAHA.107.748640Guo C, Ricchiuti V, Lian BQ, et al. Mineralocorticoid Receptor Blockade Reverses Obesity-Related Changes in Expression of Adiponectin, Peroxisome Proliferator-Activated Receptor-γ, and Proinflammatory Adipokines. Circulation. 2008;117(17):2253-2261. doi: https://doi.org/10.1161/CIRCULATIONAHA.107.748640Karashima S, Yoneda T, Kometani M, et al. Comparison of eplerenone and spironolactone for the treatment of primary aldosteronism. Hypertens Res. 2016;39(3):133-137. doi: https://doi.org/10.1038/hr.2015.129Karashima S, Yoneda T, Kometani M, et al. Comparison of eplerenone and spironolactone for the treatment of primary aldosteronism. Hypertens Res. 2016;39(3):133-137. doi: https://doi.org/10.1038/hr.2015.129Egan BM, Stepniakowski K, Goodfriend TL. Renin and aldosterone are higher and the hyperinsulinemic effect of salt restriction greater in subjects with risk factors clustering. Am J Hypertens. 1994;7(10_Pt_1):886-893. doi: https://doi.org/10.1093/ajh/7.10.886Egan BM, Stepniakowski K, Goodfriend TL. Renin and aldosterone are higher and the hyperinsulinemic effect of salt restriction greater in subjects with risk factors clustering. Am J Hypertens. 1994;7(10_Pt_1):886-893. doi: https://doi.org/10.1093/ajh/7.10.886Carroll JF, King JW, Cohen JS. Hydralazine as antihypertensive therapy in obesity-related hypertension. Int J Obes. 2004;28(3):384-390. doi: https://doi.org/10.1038/sj.ijo.0802573Carroll JF, King JW, Cohen JS. Hydralazine as antihypertensive therapy in obesity-related hypertension. Int J Obes. 2004;28(3):384-390. doi: https://doi.org/10.1038/sj.ijo.0802573de Paula RB, da Silva AA, Hall JE. Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration. Hypertension. 2004;43(1):41-47. doi: https://doi.org/10.1161/01.HYP.0000105624.68174.00de Paula RB, da Silva AA, Hall JE. Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration. Hypertension. 2004;43(1):41-47. doi: https://doi.org/10.1161/01.HYP.0000105624.68174.00Ingelsson E, Pencina MJ, Tofler GH, et al. Multimarker approach to evaluate the incidence of the metabolic syndrome and longitudinal changes in metabolic risk factors. Circulation. 2007;116(9):984-992. doi: https://doi.org/10.1161/CIRCULATIONAHA.107.708537Ingelsson E, Pencina MJ, Tofler GH, et al. Multimarker approach to evaluate the incidence of the metabolic syndrome and longitudinal changes in metabolic risk factors. Circulation. 2007;116(9):984-992. doi: https://doi.org/10.1161/CIRCULATIONAHA.107.708537Мазурина Н.В. Экзогенно-конституциональное ожирение: клинические, гормональные и биохимические параметры персонализации лечения и мониторинга. Дис. … докт. мед. наук. М.: 2020.Mazurina N.V. Exogenous-constitutional obesity: clinical, hormonal and biochemical parameters of treatment and monitoring personalization [dissertation]. Moscow: 2020. (In Russ.)Choi KM, Ryu OH, Lee KW, et al. Serum adiponectin, interleukin-10 levels and inflammatory markers in the metabolic syndrome. Diabetes Res Clin Pract. 2007;75(2):235-240. doi: https://doi.org/10.1016/j.diabres.2006.06.019Choi KM, Ryu OH, Lee KW, et al. Serum adiponectin, interleukin-10 levels and inflammatory markers in the metabolic syndrome. Diabetes Res Clin Pract. 2007;75(2):235-240. doi: https://doi.org/10.1016/j.diabres.2006.06.019Skurk T, Hauner H. Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1. Int J Obes. 2004;28(11):1357-1364. doi: https://doi.org/10.1038/sj.ijo.0802778Skurk T, Hauner H. Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1. Int J Obes. 2004;28(11):1357-1364. doi: https://doi.org/10.1038/sj.ijo.0802778Trost S, Pratley RE, Sobel BE. Impaired fibrinolysis and risk for cardiovascular disease in the metabolic syndrome and type 2 diabetes. Curr Diab Rep. 2006;6(1):47-54. doi: https://doi.org/10.1007/s11892-006-0052-5Trost S, Pratley RE, Sobel BE. Impaired fibrinolysis and risk for cardiovascular disease in the metabolic syndrome and type 2 diabetes. Curr Diab Rep. 2006;6(1):47-54. doi: https://doi.org/10.1007/s11892-006-0052-5Diehl AM, Li ZP, Lin HZ, Yang SQ. Cytokines and the pathogenesis of non-alcoholic steatohepatitis. Gut. 2005;54(2):303-306. doi: https://doi.org/10.1136/gut.2003.024935Diehl AM, Li ZP, Lin HZ, Yang SQ. Cytokines and the pathogenesis of non-alcoholic steatohepatitis. Gut. 2005;54(2):303-306. doi: https://doi.org/10.1136/gut.2003.024935Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med. 2000;343(20):1467-1476. doi: https://doi.org/10.1056/NEJM200011163432007Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med. 2000;343(20):1467-1476. doi: https://doi.org/10.1056/NEJM200011163432007Brea A, Mosquera D, Martín E, et al. Nonalcoholic Fatty Liver Disease Is Associated With Carotid Atherosclerosis. Arterioscler Thromb Vasc Biol. 2005;25(5):1045-1050. doi: https://doi.org/10.1161/01.ATV.0000160613.57985.18Brea A, Mosquera D, Martín E, et al. Nonalcoholic Fatty Liver Disease Is Associated With Carotid Atherosclerosis. Arterioscler Thromb Vasc Biol. 2005;25(5):1045-1050. doi: https://doi.org/10.1161/01.ATV.0000160613.57985.18Enomoto S. Effects of eplerenone on transcriptional factors and mRNA expression related to cardiac remodelling after myocardial infarction. Heart. 2005;91(12):1595-1600. doi: https://doi.org/10.1136/hrt.2004.046540Enomoto S. Effects of eplerenone on transcriptional factors and mRNA expression related to cardiac remodelling after myocardial infarction. Heart. 2005;91(12):1595-1600. doi: https://doi.org/10.1136/hrt.2004.046540Egan B, Papademetriou V, Wofford M, et al. Metabolic syndrome and insulin resistance in the TROPHY sub-study: Contrasting views in patients with high-normal blood pressure. Am J Hypertens. 2005;18(1):3-12. doi: https://doi.org/10.1016/j.amjhyper.2004.08.008Egan B, Papademetriou V, Wofford M, et al. Metabolic syndrome and insulin resistance in the TROPHY sub-study: Contrasting views in patients with high-normal blood pressure. Am J Hypertens. 2005;18(1):3-12. doi: https://doi.org/10.1016/j.amjhyper.2004.08.008Buglioni A, Cannone V, Sangaralingham SJ, et al. Aldosterone predicts cardiovascular, renal, and metabolic disease in the general community: A 4‐year follow‐up. J Am Heart Assoc. 2015;4(12). doi: https://doi.org/10.1161/JAHA.115.002505Buglioni A, Cannone V, Sangaralingham SJ, et al. Aldosterone predicts cardiovascular, renal, and metabolic disease in the general community: A 4‐year follow‐up. J Am Heart Assoc. 2015;4(12). doi: https://doi.org/10.1161/JAHA.115.002505Joseph JJ, Echouffo Tcheugui JB, et al. Renin‐angiotensin-aldosterone system, glucose metabolism and incident type 2 diabetes mellitus: MESA. J Am Heart Assoc. 2018;7(17). doi: https://doi.org/10.1161/JAHA.118.009890Joseph JJ, Echouffo Tcheugui JB, et al. Renin‐angiotensinaldosterone system, glucose metabolism and incident type 2 diabetes mellitus: MESA. J Am Heart Assoc. 2018;7(17). doi: https://doi.org/10.1161/JAHA.118.009890van der Heijden CDCC, ter Horst R, van den Munckhof ICL, et al. Vasculometabolic and inflammatory effects of aldosterone in obesity. J Clin Endocrinol Metab. 2020;105(8):2719-2731. doi: https://doi.org/10.1210/clinem/dgaa356van der Heijden CDCC, ter Horst R, van den Munckhof ICL, et al. Vasculometabolic and inflammatory effects of aldosterone in obesity. J Clin Endocrinol Metab. 2020;105(8):2719-2731. doi: https://doi.org/10.1210/clinem/dgaa356Varbo A, Benn M, Tybjærg-Hansen A, Nordestgaard BG. Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation. Circulation. 2013;128(12):1298-1309. doi: https://doi.org/10.1161/CIRCULATIONAHA.113.003008Varbo A, Benn M, Tybjærg-Hansen A, Nordestgaard BG. Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation. Circulation. 2013;128(12):1298-1309. doi: https://doi.org/10.1161/CIRCULATIONAHA.113.003008Van der Zijl NJ, Moors CC, Goossens GH, et al. Does interference with the renin-angiotensin system protect against diabetes? Evidence and mechanisms. Diabetes, obesity & metabolism. 2012;14(7):586-595. doi: https://doi.org/10.1111/j.1463-1326.2012.01559.xVan der Zijl NJ, Moors CC, Goossens GH, et al. Does interference with the renin-angiotensin system protect against diabetes? Evidence and mechanisms. Diabetes, obesity & metabolism. 2012;14(7):586-595. doi: https://doi.org/10.1111/j.1463-1326.2012.01559.xDREAM Trial Investigators, Bosch J, Yusuf S, et al. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006;355(15):1551-1562. doi: https://doi.org/10.1056/NEJMoa065061DREAM Trial Investigators, Bosch J, Yusuf S, et al. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006;355(15):1551-1562. doi: https://doi.org/10.1056/NEJMoa065061NAVIGATOR Study Group, McMurray JJ, Holman RR, et al. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362(16):1477-1490. doi: https://doi.org/10.1056/NEJMoa1001121NAVIGATOR Study Group, McMurray JJ, Holman RR, et al. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362(16):1477-1490. doi: https://doi.org/10.1056/NEJMoa1001121van der Zijl NJ, Moors CCM, Goossens GH, et al. Valsartan Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Glucose Metabolism. Diabetes Care. 2011;34(4):845-851. doi: https://doi.org/10.2337/dc10-2224van der Zijl NJ, Moors CCM, Goossens GH, et al. Valsartan Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Glucose Metabolism. Diabetes Care. 2011;34(4):845-851. doi: https://doi.org/10.2337/dc10-2224Sowers JR, Raij L, Jialal I, et al. Angiotensin receptor blocker/diuretic combination preserves insulin responses in obese hypertensives. J Hypertens. 2010;28(8):1761-1769. doi: https://doi.org/10.1097/HJH.0b013e32833af380Sowers JR, Raij L, Jialal I, et al. Angiotensin receptor blocker/diuretic combination preserves insulin responses in obese hypertensives. J Hypertens. 2010;28(8):1761-1769. doi: https://doi.org/10.1097/HJH.0b013e32833af380Hitomi H, Kiyomoto H, Nishiyama A, et al. Aldosterone suppresses insulin signaling via the downregulation of insulin receptor substrate-1 in vascular smooth muscle cells. Hypertension. 2007;50(4):750-755. doi: https://doi.org/10.1161/HYPERTENSIONAHA.107.093955Hitomi H, Kiyomoto H, Nishiyama A, et al. Aldosterone suppresses insulin signaling via the downregulation of insulin receptor substrate-1 in vascular smooth muscle cells. Hypertension. 2007;50(4):750-755. doi: https://doi.org/10.1161/HYPERTENSIONAHA.107.093955Bender SB, McGraw AP, Jaffe IZ, Sowers JR. Mineralocorticoid receptor–mediated vascular insulin resistance. Diabetes. 2013;62(2):313-319. doi: https://doi.org/10.2337/db12-0905Bender SB, McGraw AP, Jaffe IZ, Sowers JR. Mineralocorticoid receptor–mediated vascular insulin resistance. Diabetes. 2013;62(2):313-319. doi: https://doi.org/10.2337/db12-0905Krug AW, Stelzner L, Rao AD, et al. Effect of low dose mineralocorticoid receptor antagonist eplerenone on glucose and lipid metabolism in healthy adult males. Metabolism. 2013;62(3):386-391. doi: https://doi.org/10.1016/j.metabol.2012.08.011Krug AW, Stelzner L, Rao AD, et al. Effect of low dose mineralocorticoid receptor antagonist eplerenone on glucose and lipid metabolism in healthy adult males. Metabolism. 2013;62(3):386-391. doi: https://doi.org/10.1016/j.metabol.2012.08.011Šindelka G, Widimský J, Haas T, et al. Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment. Exp Clin Endocrinol Diabetes. 2012;108(01):21-25. doi: https://doi.org/10.1055/s-0032-1329211Šindelka G, Widimský J, Haas T, et al. nsulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment. Exp Clin Endocrinol Diabetes. 2012;108(01):21-25. doi: https://doi.org/10.1055/s-0032-1329211Catena C, Lapenna R, Baroselli S, et al. Insulin sensitivity in patients with primary aldosteronism: A follow-up study. J Clin Endocrinol Metab. 2006;91(9):3457-3463. doi: https://doi.org/10.1210/jc.2006-0736Catena C, Lapenna R, Baroselli S, et al. Insulin sensitivity in patients with primary aldosteronism: A follow-up study. J Clin Endocrinol Metab. 2006;91(9):3457-3463. doi: https://doi.org/10.1210/jc.2006-0736Davies JI, Band M, Morris A, Struthers AD. Spironolactone impairs endothelial function and heart rate variability in patients with Type 2 diabetes. Diabetologia. 2004;47(10):1687-1694. doi: https://doi.org/10.1007/s00125-004-1510-8Davies JI, Band M, Morris A, Struthers AD. Spironolactone impairs endothelial function and heart rate variability in patients with Type 2 diabetes. Diabetologia. 2004;47(10):1687-1694. doi: https://doi.org/10.1007/s00125-004-1510-8Polyzos SA, Kountouras J, Mantzoros CS, et al. Effects of combined low‐dose spironolactone plus vitamin E vs vitamin E monotherapy on insulin resistance, non‐invasive indices of steatosis and fibrosis, and adipokine levels in non‐alcoholic fatty liver disease: randomized controlled trial. Diabetes, Obes Metab. 2017;19(12):1805-1809. doi: https://doi.org/10.1111/dom.12989Polyzos SA, Kountouras J, Mantzoros CS, et al. Effects of combined low‐dose spironolactone plus vitamin E vs vitamin E monotherapy on insulin resistance, non‐invasive indices of steatosis and fibrosis, and adipokine levels in non‐alcoholic fatty liver disease: randomized controlled trial. Diabetes, Obes Metab. 2017;19(12):1805-1809. doi: https://doi.org/10.1111/dom.12989Johansen ML, Schou M, Rossignol P, et al. Effect of the mineralocorticoid receptor antagonist eplerenone on liver fat and metabolism in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial (MIRAD trial). Diabetes, Obes Metab. 2019;21(10):2305-2314. doi: https://doi.org/10.1111/dom.13809Johansen ML, Schou M, Rossignol P, et al. Effect of the mineralocorticoid receptor antagonist eplerenone on liver fat and metabolism in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial (MIRAD trial). Diabetes, Obes Metab. 2019;21(10):2305-2314. doi: https://doi.org/10.1111/dom.13809

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