{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:11:27Z","timestamp":1790655087886,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>\n                      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 (\n                      <jats:italic>CYP11B2<\/jats:italic>\n                      ) expression and aldosterone release and promotes cardiovascular dysfunction via aldosterone-dependent mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Immunostaining of human adrenal cross-sections and adrenocortical cells revealed that adrenocortical cells coexpress\n                      <jats:italic>CYP11B2<\/jats:italic>\n                      and leptin receptors. Measurements of adrenal\n                      <jats:italic>CYP11B2<\/jats:italic>\n                      expression and plasma aldosterone levels showed that increases in endogenous (obesity) or exogenous (infusion) leptin dose-dependently raised\n                      <jats:italic>CYP11B2<\/jats:italic>\n                      expression and aldosterone without elevating plasma angiotensin II, potassium or corticosterone. Neither angiotensin II receptors blockade nor \u03b1 and \u03b2 adrenergic receptors inhibition blunted leptin-induced aldosterone secretion. Identical results were obtained in cultured adrenocortical cells. Enhanced leptin signaling elevated\n                      <jats:italic>CYP11B2<\/jats:italic>\n                      expression and plasma aldosterone, whereas deficiency in leptin or leptin receptors blunted obesity-induced increases in\n                      <jats:italic>CYP11B2<\/jats:italic>\n                      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\n                      <jats:italic>CYP11B2<\/jats:italic>\n                      , in adrenocortical cells. Mineralocorticoid receptor blockade blunted leptin-induced endothelial dysfunction and increases in cardiac fibrotic markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>\n                      Leptin is a newly described regulator of aldosterone synthesis that acts directly on adrenal glomerulosa cells to increase\n                      <jats:italic>CYP11B2<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.115.018226","type":"journal-article","created":{"date-parts":[[2015,9,11]],"date-time":"2015-09-11T22:14:35Z","timestamp":1442009675000},"page":"2134-2145","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":350,"title":["Adipocyte-Derived Hormone Leptin Is a Direct Regulator of Aldosterone Secretion, Which Promotes Endothelial Dysfunction and Cardiac Fibrosis"],"prefix":"10.1161","volume":"132","author":[{"given":"Anne-C\u00e9cile","family":"Huby","sequence":"first","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Antonova","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"Groenendyk","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso E.","family":"Gomez-Sanchez","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy B.","family":"Bollag","sequence":"additional","affiliation":[{"name":"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. 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