Aldosterone Inhibitors May Improve Metabolism in Obese Patients

Dr. Eric J. Belin de Chantemèle PhD Georgia Regents University Augusta Georgia Interview with:
Dr. Eric J. Belin de Chantemèle PhD
Georgia Regents University
Augusta Georgia 

Medical Research: What is the background for this study? What are the main findings?

Response:  Obesity is currently a worldwide epidemic and a major risk factor for cardiovascular disease including among others hypertension, endothelial dysfunction, atherosclerosis and coronary artery disease. Despite decades of research, the mechanisms linking obesity to cardiovascular disease still remain incompletely understood.

Obesity is commonly associated with increased levels of the mineralocorticoid hormone aldosterone. Excessive amounts of aldosterone promote hypertension, vascular and heart disease but also lead to inflammation, and facilitate the development of diabetes. The present study aimed at deciphering the origin of these high aldosterone levels. We have been the first to demonstrate that the adipocyte derived hormone leptin controls the level of expression of the enzyme producing aldosterone: aldosterone synthase (CYP11B2), in the adrenal glands, and leptin stimulates the release of aldosterone. This was demonstrated in different mouse models as well as in cultured human adrenocortical cells. We also demonstrated that leptin-mediated aldosterone production promotes the development of cardiovascular disease, notably impairs endothelium-dependent relaxation in major arteries and promotes the development of cardiac fibrosis. Both endothelial dysfunction and cardiac fibrosis are precursors of major cardiovascular disease.

Medical Research: What should clinicians and patients take away from your report?

Response: The results for the present study are extremely important for clinicians and patients, notably due to the pleiotropic effects of aldosterone on the metabolic and cardiovascular system. If confirmed in human patients, our data would suggest that the inhibitors of aldosterone action (mineralocorticoid receptor blockers) currently available and used as the 4th line of treatment should probably be used more frequently in obese patients to improve their metabolic phenotype and notably reduce their risk for diabetes, and also to lower their risk for cardiovascular disease.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: The results of the present created a need for human studies looking at the interaction between leptin, aldosterone, and cardiovascular risk factors in human. As women secrete more leptin than men, a recommendation would be to include both sexes in these studies.


The Adipocyte-Derived Hormone Leptin is a Direct Regulator of Aldosterone Secretion, Which Promotes Endothelial Dysfunction and Cardiac Fibrosis

Anne-Cécile Huby, Galina Antonova, Jake Groenendyk, Celso E. Gomez-Sanchez, Wendy B. Bollag, Jessica A. Filosa, and Eric J. Belin de Chantemèle

Circulation. 2015;CIRCULATIONAHA.115.018226published online before print September 11 2015, doi:10.1161/CIRCULATIONAHA.115.018226

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