Adipocyte-Derived Hormone Leptin Is a Direct Regulator of Aldosterone Secretion, Which Promotes Endothelial Dysfunction and Cardiac Fibrosis
Abstract
BACKGROUND: In obesity, the excessive synthesis of aldosterone contributes to the development and progression of metabolic and cardiovascular dysfunctions. Obesity-induced hyperaldosteronism is independent of the known regulators of aldosterone secretion, but reliant on unidentified adipocyte-derived factors. We hypothesized that the adipokine leptin is a direct regulator of aldosterone synthase (CYP11B2) expression and aldosterone release and promotes cardiovascular dysfunction via aldosterone-dependent mechanisms. METHODS AND RESULTS: Immunostaining of human adrenal cross-sections and adrenocortical cells revealed that adrenocortical cells coexpress CYP11B2 and leptin receptors. Measurements of adrenal CYP11B2 expression and plasma aldosterone levels showed that increases in endogenous (obesity) or exogenous (infusion) leptin dose-dependently raised CYP11B2 expression and aldosterone without elevating plasma angiotensin II, potassium or corticosterone. Neither angiotensin II receptors blockade nor α and β adrenergic receptors inhibition blunted leptin-induced aldosterone secretion. Identical results were obtained in cultured adrenocortical cells. Enhanced leptin signaling elevated CYP11B2 expression and plasma aldosterone, whereas deficiency in leptin or leptin receptors blunted obesity-induced increases in CYP11B2 and aldosterone, ruling out a role for obesity per se. Leptin increased intracellular calcium, elevated calmodulin and calmodulin-kinase II expression, whereas calcium chelation blunted leptin-mediated increases in CYP11B2, in adrenocortical cells. Mineralocorticoid receptor blockade blunted leptin-induced endothelial dysfunction and increases in cardiac fibrotic markers. CONCLUSIONS: Leptin is a newly described regulator of aldosterone synthesis that acts directly on adrenal glomerulosa cells to increase CYP11B2 expression and enhance aldosterone production via calcium-dependent mechanisms. Furthermore, leptin-mediated aldosterone secretion contributes to cardiovascular disease by promoting endothelial dysfunction and the expression of profibrotic markers in the heart.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Leptin adversely affects calcium handling in cardiomyocytes so as to impair myocardial relaxation, stimulates the synthesis of collagen inducing cardiac fibrosis by increasing aldosterone secretion, and enhances sodium tubular reabsorption.
“Moreover, leptin adversely affects calcium handling in cardiomyocytes so as to impair myocardial relaxation, stimulates the synthesis of collagen inducing cardiac fibrosis by increasing aldosterone secretion, and enhances the sodium tubular reabsorption [95,96,97].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [96]
Cites
PTP1B Regulates Leptin Signal Transduction In Vivo
Zabolotny, J. M., Bence, K. K., Stricker‐Krongrad, A., Haj, F. G., Wang, Y., Minokoshi, Y., Kim, Y., Elmquist, J. K., Tartaglia, L. A., Kahn, B. B., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00148-x · Cited by 816 · see citing works
Ozata, M., Ozdemir, I. C., & Licinio, J. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.5999 · Cited by 739 · see citing works
Abel, E. D., Litwin, S. E., & Sweeney, G. (2008) · Physiological Reviews · doi:10.1152/physrev.00017.2007 · Cited by 736 · see citing works
Attenuation of Leptin Action and Regulation of Obesity by Protein Tyrosine Phosphatase 1B
Cheng, A., Uetani, N., Simoncic, P. D., Chaubey, V. P., Lee-Loy, A., McGlade, C. J., Kennedy, B. P., & Tremblay, M. L. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00149-1 · Cited by 539 · see citing works
Obesity-induced Hypertension: Role of Sympathetic Nervous System, Leptin, and Melanocortins
Hall, J. E., da Silva, A. A., do Carmo, J. M., Dubinion, J., Hamza, S., Munusamy, S., Smith, G., & Stec, D. E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r110.113175 · Cited by 528 · see citing works
Control of aldosterone secretion: a model for convergence in cellular signaling pathways
SPÄT, A., & HUNYADY, L. (2004) · Physiological Reviews · doi:10.1152/physrev.00030.2003 · Cited by 494 · see citing works
Human adipocytes secrete mineralocorticoid-releasing factors
Ehrhart‐Bornstein, M., Lamounier‐Zepter, V., Schraven, A., Langenbach, J., Willenberg, H. S., Barthel, A., Hauner, H., McCann, S. M., Scherbaum, W. A., & Bornstein, S. R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2336140100 · Cited by 443 · see citing works
Briones, A. M., Nguyen Dinh Cat, A., Callera, G. E., Yogi, A., Burger, D., He, Y., Corrêa, J. W., Gagnon, A. M., Gomez-Sanchez, C. E., Gomez-Sanchez, E. P., et al. (2012) · Hypertension · doi:10.1161/hypertensionaha.111.190223 · Cited by 375 · see citing works
Sixteen years and counting: an update on leptin in energy balance
Gautron, L., & Elmquist, J. K. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45888 · Cited by 367 · see citing works
Sowers, J. R., Whaley-Connell, A., & Epstein, M. (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-150-11-200906020-00005 · Cited by 351 · see citing works
Acute and chronic regulation of aldosterone production
Hattangady, N. G., Olala, L. O., Bollag, W. B., & Rainey, W. E. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.07.034 · Cited by 347 · see citing works
Guo, C., Ricchiuti, V., Lian, B. Q., Yao, T. M., Coutinho, P., Romero, J. R., Li, J., Williams, G. H., & Adler, G. K. (2008) · Circulation · doi:10.1161/circulationaha.107.748640 · Cited by 342 · see citing works
Klebig, M. L., Wilkinson, J. E., Geisler, J. G., & Woychik, R. P. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.11.4728 · Cited by 290 · see citing works
Development of monoclonal antibodies against human CYP11B1 and CYP11B2
Gómez-Sánchez, C. E., Qi, X., Velarde‐Miranda, C., Plonczynski, M. W., Parker, C. R., Rainey, W. E., Satoh, F., Maekawa, T., Nakamura, Y., Sasano, H., et al. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.11.022 · Cited by 283 · see citing works
Enhanced Aldosterone Signaling in the Early Nephropathy of Rats with Metabolic Syndrome
Nagase, M., Yoshida, S., Shibata, S., Nagase, T., Gotoda, T., Ando, K., & Fujita, T. (2006) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006080944 · Cited by 247 · see citing works
Plasma aldosterone is independently associated with the metabolic syndrome
Bochud, M., Nussberger, J., Bovet, P., Maillard, M. R., Elston, R. C., Paccaud, F., Shamlaye, C., & Burnier, M. (2006) · Hypertension · doi:10.1161/01.hyp.0000231338.41548.fc · Cited by 226 · see citing works
Selective leptin resistance: a new concept in leptin physiology with cardiovascular implications
Mark, A. L., Correia, M. L. G., Rahmouni, K., & Haynes, W. G. (2002) · Journal of Hypertension · doi:10.1097/00004872-200207000-00001 · Cited by 215 · see citing works
Association of Adrenal Steroids With Hypertension and the Metabolic Syndrome in Blacks
Kidambi, S., Kotchen, J. M., Grim, C. E., Raff, H., Mao, J., Singh, R., & Kotchen, T. A. (2006) · Hypertension · doi:10.1161/01.hyp.0000253258.36141.c7 · Cited by 212 · see citing works
Role of Calcium in Angiotensin II-Mediated Aldosterone Secretion*
BARRETT, P. Q., BOLLAG, W. B., ISALES, C. M., MCCARTHY, R. T., & RASMUSSEN, H. (1989) · Endocrine Reviews · doi:10.1210/edrv-10-4-496 · Cited by 183 · see citing works
Guo, C., Martinez-Vasquez, D., Méndez, G. P., Toniolo, M. F., Yao, T. M., Oestreicher, E. M., Kikuchi, T., Lapointe, N., Pojoga, L. H., Williams, G. H., et al. (2006) · Endocrinology · doi:10.1210/en.2006-0944 · Cited by 174 · see citing works
Armani, A., Cinti, F., Marzolla, V., Morgan, J., Cranston, G. A., Antelmi, A., Carpinelli, G., Canese, R., Pagotto, U., Quarta, C., et al. (2014) · The FASEB Journal · doi:10.1096/fj.13-245415 · Cited by 168 · see citing works
Glasow, A., Haidan, A., Hilbers, U., Breidert, M., Gillespie, J., Scherbaum, W. A., Chrousos, G. P., & Bornstein, S. R. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.12.5337 · Cited by 162 · see citing works
Aldosterone: Role in the Cardiometabolic Syndrome and Resistant Hypertension
Whaley‐Connell, A. T., Johnson, M. S., & Sowers, J. R. (2010) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2009.12.004 · Cited by 152 · see citing works
Efficacy of a leptin receptor antagonist peptide in a mouse model of triple-negative breast cancer
Otvos, L. J., Kovalszky, I., Riolfi, M., Ferla, R., Oláh, J., Sztodola, A., Nama, K., Molino, A., Piubello, Q., Wade, J. D., et al. (2011) · European Journal of Cancer · doi:10.1016/j.ejca.2011.01.018 · Cited by 115 · see citing works
Role for aldosterone in blood pressure regulation of obese adolescents
Rocchini, A. P., Katch, V. L., Grekin, R. J., Moorehead, C., & Anderson, J. (1986) · The American Journal of Cardiology · doi:10.1016/0002-9149(86)90845-3 · Cited by 112 · see citing works
Arterial Pressure, Left Ventricular Mass, and Aldosterone in Essential Hypertension
El‐Gharbawy, A., NADIG, V., Kotchen, J. M., Grim, C. E., Sagar, K. B., Kaldunski, M. L., Hamet, P., Pausová, Z., Gaudet, D., Gossard, F., et al. (2001) · Hypertension · doi:10.1161/01.hyp.37.3.845 · Cited by 108 · see citing works
Increased renal Na-K-ATPase, NCC, and β-ENaC abundance in obese Zucker rats
Bickel, C. A., Verbalis, J. G., Knepper, M. A., & ECELBARGER, C. A. (2001) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.2001.281.4.f639 · Cited by 107 · see citing works
Congenital leptin deficiency: diagnosis and effects of leptin replacement therapy
Paz-Filho, G., Mastronardi, C. A., Delibaşı, T., Wong, M., & Licinio, J. (2010) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302010000800005 · Cited by 104 · see citing works
Impact of Leptin-Mediated Sympatho-Activation on Cardiovascular Function in Obese Mice
Belin de Chantemèle, E. J., Mintz, J. D., Rainey, W. E., & Stepp, D. W. (2011) · Hypertension · doi:10.1161/hypertensionaha.110.168427 · Cited by 103 · see citing works
Development of an Adrenocorticotropin-Responsive Human Adrenocortical Carcinoma Cell Line
Parmar, J., Key, R. E., & Rainey, W. E. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0903 · Cited by 102 · see citing works
Leptin and mechanisms of endothelial dysfunction and cardiovascular disease
Knudson, J. D., Payne, G. A., Borbouse, L., & Tune, J. D. (2008) · Current Hypertension Reports · doi:10.1007/s11906-008-0082-2 · Cited by 88 · see citing works
Hyperaldosteronism and Hypertension
Grim, C. E., Cowley, A. W., Hamet, P., Gaudet, D., Kaldunski, M. L., Kotchen, J. M., Krishnaswami, S., Pausová, Z., Roman, R., Tremblay, J., et al. (2005) · Hypertension · doi:10.1161/01.hyp.0000154364.00763.d5 · Cited by 88 · see citing works
Ehrhart‐Bornstein, M., Arakelyan, K., Krug, A. W., Scherbaum, W. A., & Bornstein, S. R. (2004) · Endocrine Research · doi:10.1081/erc-200044122 · Cited by 80 · see citing works
The Role of Aldosteronism in Causing Obesity-Related Cardiovascular Risk
Calhoun, D. A., & Sharma, K. (2010) · Cardiology Clinics · doi:10.1016/j.ccl.2010.04.001 · Cited by 74 · see citing works
Belin de Chantemèle, E. J., Muta, K., Mintz, J., Tremblay, M. L., Marrero, M. B., Fulton, D. J., & Stepp, D. W. (2009) · Circulation · doi:10.1161/circulationaha.109.853077 · Cited by 67 · see citing works
Leptin’s regulation of obesity-induced cardiac extracellular matrix remodeling
Zibadi, S., Cordova-Marks, F. M., Slack, E. H., WATSON, R. R., & Larson, D. F. (2011) · Cardiovascular Toxicology · doi:10.1007/s12012-011-9124-0 · Cited by 66 · see citing works
Changes in Endocrine Activities Relative to Obesity in Patients with Essential Hypertension*
Hiramatsu, K., Yamada, T., Ichikawa, K., Izumiyama, T., & Nagata, H. (1981) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1981.tb02389.x · Cited by 55 · see citing works
Takeda, M., Tatsumi, T., Matsunaga, S., Hayashi, H., Kimata, M., Honsho, S., Nishikawa, S., Mano, A., Shiraishi, J., Yamada, H., et al. (2007) · Hypertension Research · doi:10.1291/hypres.30.427 · Cited by 55 · see citing works
Moraes, C. D. H., Figueiredo, V. N., de Faria, A. P., Barbaro, N. R., Sabbatini, A. R., Quinaglia, T., Ferreira‐Melo, S. E., Martins, L. C., Demacq, C., & Júnior, H. M. (2012) · Journal of Human Hypertension · doi:10.1038/jhh.2012.29 · Cited by 47 · see citing works
Takekoshi, K., Ishii, K., Kawakami, Y., Isobe, K., Nanmoku, T., & Nakai, T. (2001) · Endocrinology · doi:10.1210/endo.142.1.7914 · Cited by 43 · see citing works
Regulation of Catecholamine Synthesis by Leptin
Shibuya, I., Utsunomiya, K., Toyohira, Y., Ueno, S., Tsutsui, M., Cheah, T. B., Ueta, Y., Izumi, F., & Yanagihara, N. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04517.x · Cited by 40 · see citing works
Preventing increased blood pressure in the obese Zucker rat improves severity of stroke
Osmond, J. M., MINTZ, J. D., & Stepp, D. W. (2010) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01111.2009 · Cited by 37 · see citing works
Aldosterone infusion with high-NaCl diet increases blood pressure in obese but not lean Zucker rats
Riazi, S., Khan, O. A., Hu, X., & ECELBARGER, C. A. (2006) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00508.2005 · Cited by 35 · see citing works
Iddings, J. A., Kim, K., Zhou, Y., Higashimori, H., & Filosa, J. A. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.31 · Cited by 31 · see citing works
de Chantemèle, E. J. B., Ali, M. I., Mintz, J. D., Rainey, W. E., Tremblay, M. L., Fulton, D. J., & Stepp, D. W. (2012) · Hypertension · doi:10.1161/hypertensionaha.112.196295 · Cited by 25 · see citing works
Oki, K., Kopf, P. G., Campbell, W. B., Lam, M. L., Yamazaki, T., Gómez-Sánchez, C. E., & Gómez-Sánchez, E. P. (2012) · Endocrinology · doi:10.1210/en.2012-1557 · Cited by 23 · see citing works
Müller‐Fielitz, H., Lau, M., Jöhren, O., Stellmacher, F., Schwaninger, M., & Raasch, W. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01953.x · Cited by 22 · see citing works
Clapham, J. C., & Turner, N. C. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36928-9 · Cited by 21 · see citing works
Aldosterone and Metabolic Dysfunction
Pimenta, E., & Calhoun, D. A. (2009) · Hypertension · doi:10.1161/hypertensionaha.108.123406 · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Packer, M. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.03.509 · Cited by 656 · see citing works
Sex-specific differences in hypertension and associated cardiovascular disease
Colafella, K. M. M., & Denton, K. M. (2018) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.189 · Cited by 493 · see citing works
Borlaug, B. A., Jensen, M. D., Kitzman, D. W., Lam, C. S. P., Obokata, M., & Rider, O. J. (2023) · Cardiovascular Research · doi:10.1093/cvr/cvac120 · Cited by 450 · see citing works
Hypertension in Diabetes: An Update of Basic Mechanisms and Clinical Disease
Jia, G., & Sowers, J. R. (2021) · Hypertension · doi:10.1161/hypertensionaha.121.17981 · Cited by 459 · see citing works
Vanhoutte, P. M., Zhao, Y., Xu, A., & Leung, S. W. S. (2016) · Circulation Research · doi:10.1161/circresaha.116.306531 · Cited by 391 · see citing works
Diagnosis and treatment of primary aldosteronism
Reincke, M., Bancos, I., Mulatero, P., Scholl, U. I., Stowasser, M., & Williams, T. A. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00210-2 · Cited by 369 · see citing works
Cardiac fibrosis: Myofibroblast-mediated pathological regulation and drug delivery strategies
Liu, M., Abad, B. L. D. J., & Cheng, K. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.03.021 · Cited by 353 · see citing works
Treatment of Resistant and Refractory Hypertension
Acelajado, M. C., Hughes, Z. H., Oparil, S., & Calhoun, D. A. (2019) · Circulation Research · doi:10.1161/circresaha.118.312156 · Cited by 219 · see citing works
Mao, R., Kurada, S. V., Gordon, I. O., Baker, M. E., Gandhi, N. S., McDonald, C., Coffey, J. C., & Rieder, F. (2018) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izy331 · Cited by 204 · see citing works
Packer, M., Lam, C. S. P., Lund, L. H., Maurer, M. S., & Borlaug, B. A. (2020) · European Journal of Heart Failure · doi:10.1002/ejhf.1902 · Cited by 185 · see citing works
The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction
Packer, M. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.06.055 · Cited by 190 · see citing works
Lakkis, J. I., & Weir, M. R. (2018) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2018.07.005 · Cited by 181 · see citing works
Role of Leptin in Cardiovascular Diseases
Poetsch, M. S., Strano, A., & Guan, K. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00354 · Cited by 173 · see citing works
Obesity-Related Heart Failure With a Preserved Ejection Fraction
Packer, M., & Kitzman, D. W. (2018) · JACC: Heart Failure · doi:10.1016/j.jchf.2018.01.009 · Cited by 172 · see citing works
Huby, A.-C., Otvos, L. J., & de Chantemèle, E. J. B. (2016) · Hypertension · doi:10.1161/hypertensionaha.115.06642 · Cited by 168 · see citing works
The Role of Aldosterone in Obesity-Related Hypertension
Kawarazaki, W., & Fujita, T. (2016) · American Journal of Hypertension · doi:10.1093/ajh/hpw003 · Cited by 167 · see citing works
Schütten, M. T. J., Houben, A. J. H. M., de Leeuw, P. W., & Stehouwer, C. D. A. (2017) · Physiology · doi:10.1152/physiol.00037.2016 · Cited by 166 · see citing works
Stowasser, M., & Gordon, R. D. (2016) · Physiological Reviews · doi:10.1152/physrev.00026.2015 · Cited by 159 · see citing works
Association of metabolic syndrome and chronic kidney disease
Scurt, F. G., Ganz, M. J., Herzog, C., Bose, K., Mertens, P. R., & Chatzikyrkou, C. (2024) · Obesity Reviews · doi:10.1111/obr.13649 · Cited by 155 · see citing works
Hypertension in Obesity and the Impact of Weight Loss
Cohen, J. B. (2017) · Current Cardiology Reports · doi:10.1007/s11886-017-0912-4 · Cited by 147 · see citing works
Obesity and cardiovascular disease in women
Manrique‐Acevedo, C., Chinnakotla, B., Padilla, J., Martinez‐Lemus, L. A., & Gozal, D. (2020) · International Journal of Obesity · doi:10.1038/s41366-020-0548-0 · Cited by 142 · see citing works
Sex Differences in Mechanisms of Hypertension Associated With Obesity
Faulkner, J., & de Chantemèle, E. J. B. (2017) · Hypertension · doi:10.1161/hypertensionaha.117.09980 · Cited by 136 · see citing works
Regional Adiposity and Heart Failure with Preserved Ejection Fraction
Rao, V. N., Fudim, M., Mentz, R. J., Michos, E. D., & Felker, G. M. (2020) · European Journal of Heart Failure · doi:10.1002/ejhf.1956 · Cited by 131 · see citing works
Primary Aldosteronism: State-of-the-Art Review
Vaidya, A., Hundemer, G. L., Nanba, K., Parksook, W. W., & Brown, J. M. (2022) · American Journal of Hypertension · doi:10.1093/ajh/hpac079 · Cited by 135 · see citing works
Essential role of ICAM-1 in aldosterone-induced atherosclerosis
Marzolla, V., Armani, A., Mammi, C., Moss, M. E., Pagliarini, V., Pontecorvo, L., Antelmi, A., Fabbri, A., Rosano, G. M. C., Jaffe, I. Z., et al. (2017) · International Journal of Cardiology · doi:10.1016/j.ijcard.2017.01.013 · Cited by 123 · see citing works
Sex hormones, aging and cardiometabolic syndrome
Faulkner, J., & de Chantemèle, E. J. B. (2019) · Biology of Sex Differences · doi:10.1186/s13293-019-0246-6 · Cited by 124 · see citing works
Hypertension as a Metabolic Disorder and the Novel Role of the Gut
Tanaka, M., & Itoh, H. (2019) · Current Hypertension Reports · doi:10.1007/s11906-019-0964-5 · Cited by 118 · see citing works
Packer, M. (2021) · JACC Heart Failure · doi:10.1016/j.jchf.2021.05.019 · Cited by 116 · see citing works
Obesity-induced Cognitive Impairment in Older Adults: a Microvascular Perspective.
Balasubramanian, P., Kiss, T., Tarantini, S., Nyúl-Tóth, Á., Ahire, C., Yabluchanskiy, A., Csípő, T., Lipécz, Á., Tabák, Á., Institoris, A., et al. (2020) · American Journal of Physiology. Heart and Circulatory Physiology · doi:10.1152/ajpheart.00736.2020 · Cited by 106 · see citing works
Improving obesity and blood pressure
Tanaka, M. (2019) · Hypertension Research · doi:10.1038/s41440-019-0348-x · Cited by 110 · see citing works
Packer, M. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.119.015343 · Cited by 110 · see citing works
Mesenchymal stem cells in fibrotic diseases—the two sides of the same coin
Qin, L., Liu, N., Bao, C.-L.-M., Yang, D.-Z., Ma, G.-X., Yi, W.-H., Xiao, G.-Z., & Cao, H.-L. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-022-00952-0 · Cited by 114 · see citing works
Epstein, M., Kovesdy, C. P., Clase, C. M., Sood, M. M., & Pecoits‐Filho, R. (2022) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2022.04.016 · Cited by 114 · see citing works
Liu, J., Yang, X., Yu, S., & Zheng, R. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1286-1_8 · Cited by 110 · see citing works
DuPont, J. J., & Jaffe, I. Z. (2017) · Journal of Endocrinology · doi:10.1530/joe-17-0009 · Cited by 104 · see citing works
Packer, M. (2018) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13229 · Cited by 101 · see citing works
Adipocytes, aldosterone and obesity-related hypertension
Cat, A. N. D., Friederich‐Persson, M., White, A. D., & Touyz, R. M. (2016) · Journal of Molecular Endocrinology · doi:10.1530/jme-16-0025 · Cited by 96 · see citing works
Hill, M. A., Jaisser, F., & Sowers, J. R. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa326 · Cited by 90 · see citing works
Biomarkers to Guide Medical Therapy in Primary Aldosteronism
Hundemer, G. L., Leung, A. A. C., Kline, G. A., Brown, J. M., Turcu, A. F., & Vaidya, A. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad024 · Cited by 89 · see citing works
Mechanisms and treatment of obesity-related hypertension—Part 1: Mechanisms
Parvanova, A. I., Reseghetti, E., Abbate, M., & Ruggenenti, P. L. (2023) · Clinical Kidney Journal · doi:10.1093/ckj/sfad282 · Cited by 98 · see citing works
Obesity and the kidney: mechanistic links and therapeutic advances
Yau, K., Kuah, R., Cherney, D. Z. I., & Lam, T. K. T. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-00951-7 · Cited by 91 · see citing works
Anti-Inflammatory Effects of Melatonin in Obesity and Hypertension
Prado, N. J., Ferder, L., Manucha, W. A., & Diez, E. R. (2018) · Current Hypertension Reports · doi:10.1007/s11906-018-0842-6 · Cited by 85 · see citing works
Faulkner, J., Kennard, S., Huby, A.-C., Antonova, G. N., Lu, Q. R., Jaffe, I. Z., Patel, V. S., Fulton, D. J., & de Chantemèle, E. J. B. (2019) · Hypertension · doi:10.1161/hypertensionaha.119.12802 · Cited by 84 · see citing works
Mineralocorticoid Receptors in Metabolic Syndrome: From Physiology to Disease
Feraco, A., Marzolla, V., Scuteri, A., Armani, A., & Caprio, M. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.11.006 · Cited by 83 · see citing works
The regulation of aldosterone secretion by leptin
Faulkner, J., Bruder-Nascimento, T. B., & de Chantemèle, E. J. B. (2017) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000384 · Cited by 85 · see citing works
Obesity as a Key Factor Underlying Idiopathic Hyperaldosteronism
Ohno, Y., Sone, M., Inagaki, N., Yamasaki, T., Ogawa, O., Takeda, Y., Kurihara, I., Umakoshi, H., Ichijo, T., Katabami, T., et al. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00866 · Cited by 75 · see citing works
Weight Loss Medications in the Treatment of Obesity and Hypertension
Cohen, J. B., & Gadde, K. M. (2019) · Current Hypertension Reports · doi:10.1007/s11906-019-0915-1 · Cited by 80 · see citing works
Kawabe, Y., Mori, J., Morimoto, H., Yamaguchi, M., Miyagaki, S., Ota, T., Tsuma, Y., Fukuhara, S., Nakajima, H., Oudit, G. Y., et al. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00311.2019 · Cited by 74 · see citing works
FKBP51 and the molecular chaperoning of metabolism
Smedlund, K., Sánchez, E. R., & Hinds, T. D. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.08.003 · Cited by 73 · see citing works
Is Primary Aldosteronism Still Largely Unrecognized?
Buffolo, F., Monticone, S., Burrello, J., Tetti, M., Veglio, F., Williams, T. A., & Mulatero, P. (2017) · Hormone and Metabolic Research · doi:10.1055/s-0043-119755 · Cited by 74 · see citing works
Kidney and epigenetic mechanisms of salt-sensitive hypertension
Kawarazaki, W., & Fujita, T. (2021) · Nature Reviews Nephrology · doi:10.1038/s41581-021-00399-2 · Cited by 73 · see citing works
Aldosterone-Regulated Sodium Transport and Blood Pressure
Tsilosani, A., Gao, C., & Zhang, W. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.770375 · Cited by 72 · see citing works
How does obesity affect the endocrine system? A narrative review
Poddar, M., Chetty, Y., & Chetty, V. T. (2017) · Clinical Obesity · doi:10.1111/cob.12184 · Cited by 69 · see citing works
Obesity, hypertension and aldosterone: is leptin the link?
Xie, D., & Bollag, W. B. (2016) · Journal of Endocrinology · doi:10.1530/joe-16-0160 · Cited by 69 · see citing works
Jia, G., Aroor, A. R., & Sowers, J. R. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx097 · Cited by 69 · see citing works
Obesity-associated cardiovascular risk in women: hypertension and heart failure
Faulkner, J. (2021) · Clinical Science · doi:10.1042/cs20210384 · Cited by 69 · see citing works
Aldosterone and cardiovascular diseases
Parksook, W. W., & Williams, G. H. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac027 · Cited by 68 · see citing works
The Effect of Aldosterone on Cardiorenal and Metabolic Systems
Otsuka, H., Abe, M., & Kobayashi, H. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065370 · Cited by 68 · see citing works
Aging and Adrenal Aldosterone Production
Nanba, K., Vaidya, A., & Rainey, W. E. (2017) · Hypertension · doi:10.1161/hypertensionaha.117.10391 · Cited by 66 · see citing works
The Role of Aldosterone in OSA and OSA-Related Hypertension
Wang, Y., Li, C. X., Lin, Y. N., Zhang, L. Y., Li, S. Q., Zhang, L., Yan, Y. R., Lu, F., Li, N., & Li, Q. Y. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.801689 · Cited by 65 · see citing works
Salvatore, T., Galiero, R., Caturano, A., Vetrano, E., Rinaldi, L., Coviello, F., Di Martino, A., Albanese, G., Colantuoni, S., Medicamento, G., et al. (2022) · Biomolecules · doi:10.3390/biom12020176 · Cited by 62 · see citing works
Female Sex, a Major Risk Factor for Salt-Sensitive Hypertension
Faulkner, J., & de Chantemèle, E. J. B. (2020) · Current Hypertension Reports · doi:10.1007/s11906-020-01113-6 · Cited by 61 · see citing works
Understanding the Pathobiology of Pulmonary Hypertension Due to Left Heart Disease
Huston, J., & Shah, S. J. (2022) · Circulation Research · doi:10.1161/circresaha.122.319967 · Cited by 61 · see citing works
Aldosterone Production and Signaling Dysregulation in Obesity
Vecchiola, A., Lagos, C. F., Carvajal, C. A., Baudrand, R. F., & Fardella, C. (2016) · Current Hypertension Reports · doi:10.1007/s11906-016-0626-9 · Cited by 61 · see citing works
Packer, M. (2018) · European Journal of Heart Failure · doi:10.1002/ejhf.1167 · Cited by 61 · see citing works
JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target
Jiang, H., Yang, J., Li, T., Wang, X., Fan, Z., Ye, Q., & Du, Y. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1336102 · Cited by 61 · see citing works
Faulkner, J., Harwood, D., Bender, L., Shrestha, L., Brands, M. W., Morwitzer, M. J., Kennard, S., Antonova, G. N., & de Chantemèle, E. J. B. (2018) · Hypertension · doi:10.1161/hypertensionaha.118.11303 · Cited by 58 · see citing works
Hypertensive Heart Disease and Obesity
Saliba, L. J., & Maffett, S. (2019) · Heart Failure Clinics · doi:10.1016/j.hfc.2019.06.003 · Cited by 58 · see citing works
The Vascular Involvement in Soft Tissue Fibrosis—Lessons Learned from Pathological Scarring
Huang, C., & Ogawa, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072542 · Cited by 58 · see citing works
Pathophysiology and genetics of salt-sensitive hypertension
Maaliki, D. S., Itani, M. M., & Itani, H. A. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.1001434 · Cited by 60 · see citing works
Body Mass Index Predicts 24-Hour Urinary Aldosterone Levels in Patients With Resistant Hypertension
Dudenbostel, T., Ghazi, L., Liu, M., Li, P., Oparil, S., & Calhoun, D. A. (2016) · Hypertension · doi:10.1161/hypertensionaha.116.07806 · Cited by 58 · see citing works
Patel, R. B., Colangelo, L. A., Bielinski, S. J., Larson, N. B., Ding, J., Allen, N. B., Michos, E. D., Shah, S. J., & Lloyd‐Jones, D. M. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.120.019390 · Cited by 56 · see citing works
Mechano-energetic uncoupling in heart failure
Aksentijević, D., Sedej, S., Fauconnier, J., Paillard, M., Abdellatif, M., Streckfuß‐Bömeke, K., Ventura‐Clapier, R., van der Velden, J., de Boer, R. A., Bertero, E., et al. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-025-01167-6 · Cited by 55 · see citing works
Foxc2 coordinates inflammation and browning of white adipose by leptin-STAT3-PRDM16 signal in mice
Gan, L., Liu, Z., Feng, F., Wu, T., Luo, D., Hu, C. Y., & Sun, C. (2017) · International Journal of Obesity · doi:10.1038/ijo.2017.208 · Cited by 52 · see citing works
Impact of Adrenal Steroids on Regulation of Adipose Tissue
Infante, M., Armani, A., Mammi, C., Fabbri, A., & Caprio, M. (2017) · Comprehensive physiology · doi:10.1002/cphy.c160037 · Cited by 52 · see citing works
Linking Arrhythmias and Adipocytes: Insights, Mechanisms, and Future Directions
Pabón, M. A., Manocha, K. K., Cheung, J. W., & Lo, J. C. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01752 · Cited by 48 · see citing works
Ghafar, M. T. A. (2020) · Steroids · doi:10.1016/j.steroids.2020.108701 · Cited by 50 · see citing works
Cardiopulmonary Dysfunction and Adiponectin in Adolescents With Type 2 Diabetes
Bjornstad, P., Truong, U. T., Dorosz, J. L., Cree‐Green, M., Baumgartner, A., Coe, G. V., Pyle, L., Regensteiner, J. G., Reusch, J. E. B., & Nadeau, K. J. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.115.002804 · Cited by 47 · see citing works
(2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.07.012 · Cited by 46 · see citing works
Links between aldosterone excess and metabolic complications: A comprehensive review
Bothou, C., Beuschlein, F., & Spyroglou, A. (2019) · Diabetes & Metabolism · doi:10.1016/j.diabet.2019.02.003 · Cited by 46 · see citing works
Kobayashi, M., Pitt, B., Ferreira, J. P., Rossignol, P., Girerd, N., & Zannad, F. M. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf225 · Cited by 50 · see citing works
Evaluation of the pathophysiological mechanisms of salt-sensitive hypertension
Hirohama, D., & Fujita, T. (2019) · Hypertension Research · doi:10.1038/s41440-019-0332-5 · Cited by 43 · see citing works
Wiegel, R. E., Danser, A. H. J., Steegers‐Theunissen, R. P. M., Laven, J. S. E., Willemsen, S. P., Baker, V. L., Steegers, E. A. P., & von Versen‐Höynck, F. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa582 · Cited by 44 · see citing works
Jia, G., Lockette, W. E., & Sowers, J. R. (2021) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00280.2020 · Cited by 45 · see citing works
Obesity: The Perfect Storm for Heart Failure
Lembo, M., Strisciuglio, T., Fonderico, C., Mancusi, C., Izzo, R., Trimarco, V., Bellis, A., Barbato, E., Esposito, G., Morisco, C., et al. (2024) · ESC Heart Failure · doi:10.1002/ehf2.14641 · Cited by 46 · see citing works
Sex differences in sympathetic activity in obesity and its related hypertension
Fu, Q. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14095 · Cited by 42 · see citing works
Hu, Y., Zhang, J., Liu, W., & Su, X. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz293 · Cited by 42 · see citing works
The Mineralocorticoid Receptor in Salt-Sensitive Hypertension and Renal Injury
Ayuzawa, N., & Fujita, T. (2021) · Journal of the American Society of Nephrology · doi:10.1681/asn.2020071041 · Cited by 41 · see citing works
Chen, J., Mei, Z., Yang, Y., Dai, C., Wang, Y., Zeng, R., & Liu, Q. (2022) · BMC Cardiovascular Disorders · doi:10.1186/s12872-022-02703-9 · Cited by 41 · see citing works
da Costa, R. M., Cerqueira, D. M., Bruder‐Nascimento, A., Alves, J. V., Awata, W. M. C., Singh, S., Kufner, A., Prado, D. D. S., Johny, E., Cifuentes-Pagano, E., et al. (2024) · Hypertension · doi:10.1161/hypertensionaha.123.21888 · Cited by 40 · see citing works
Normotension, hypertension and body fluid regulation: brain and kidney
Bie, P., & Evans, R. G. (2016) · Acta Physiologica · doi:10.1111/apha.12718 · Cited by 40 · see citing works
Mechanisms of leptin-induced endothelial dysfunction
Mellott, E., & Faulkner, J. (2022) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000867 · Cited by 39 · see citing works
Crum, Y., Hoendermis, E. S., van Veldhuisen, D. J., van Woerden, G., Lobeek, M., Dickinson, M. G., Meems, L. M. G., Voors, A. A., Rienstra, M., & Gorter, T. M. (2024) · ESC Heart Failure · doi:10.1002/ehf2.14739 · Cited by 39 · see citing works
The endothelial mineralocorticoid receptor
Davel, A. P., Anwar, I. J., & Jaffe, I. Z. (2016) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000306 · Cited by 39 · see citing works
Gan, L., Liu, Z., Luo, D., Ren, Q., Wu, H., Li, C., & Sun, C. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01507 · Cited by 38 · see citing works
Gutiérrez-Tenorio, J., Marín‐Royo, G., Martínez‐Martínez, E., Martín, R., Miana, M., López‐Andrés, N., Jurado-López, R., Gallardo, I., Luaces, M., Román, J. A. S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17103-9 · Cited by 38 · see citing works
Davel, A. P., Jaffe, I. Z., Tostes, R. C., Jaisser, F., & de Chantemèle, E. J. B. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00073.2018 · Cited by 39 · see citing works
Tao, Z., Zuo, P., & Ma, G. (2024) · Scientific Reports · doi:10.1038/s41598-024-69486-1 · Cited by 37 · see citing works
Bruder-Nascimento, T. B., Faulkner, J., Haigh, S. B., Kennard, S., Antonova, G. N., Patel, V. S., Fulton, D. J., Chen, W., & de Chantemèle, E. J. B. (2019) · Hypertension · doi:10.1161/hypertensionaha.119.13398 · Cited by 37 · see citing works
- Authors
- Huby, A.-C., Antonova, G., Groenendyk, J., Gomez-Sanchez, C. E., Bollag, W. B., Filosa, J. A., & de Chantemèle, E. J. B.
- Affiliations
- Augusta University (US)
- From Physiology Department, Medical College of Georgia at Georgia Regents University, Augusta (A.-C.H., G.A., J.G., W.B.B., J.A.F., E.J.D.d.C.); Charlie Norwood VA Medical Center, Augusta, GA (W.B.B.); Endocrine Section, G.V. (Sonny) Montgomery VA Medical Center, and University of Mississippi Medical Center, Jackson (C..E.G.-S.).
- Venue
- Circulation
- Published
- 2015-12
- Volume
- 132
- Issue
- 22
- Pages
- 2134-2145
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2206025985
- Cited by
- 376
- References
- 49
- Citations by year
- 2026: 34 · 2025: 41 · 2024: 37 · 2023: 34 · 2022: 44 · 2021: 32 · 2020: 36 · 2019: 31 · 2018: 37 · 2017: 29 · 2016: 18 · 2015: 1 · 2012: 1
- FWCI
- 24.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, aldosterone secretion, CYP11B2, aldosterone synthase, obesity, hyperaldosteronism, adrenal glomerulosa cells, adipokines, endothelial dysfunction, myocardial fibrosis, calcium signaling, calcium/calmodulin-dependent protein kinase II, mineralocorticoid receptor, cardiovascular disease
- MeSH terms
- Adrenal Cortex, Aldosterone, Animals, Cells, Cultured, Endothelium, Vascular, Female, Fibrosis, Heart Diseases, Humans, Mice, Inbred C57BL, Mice, Obese, Rats, Inbred WKY, Rats, Zucker, Adipocytes, Mice, Knockout, Leptin, Cell Line, Tumor, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
