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Hypertension. 2015 Jul;66(1):149-57. doi: 10.1161/HYPERTENSIONAHA.114.04981. Epub 2015 May 11.

Adipocyte Mineralocorticoid Receptor Activation Leads to Metabolic Syndrome and Induction of Prostaglandin D2 Synthase.

Author information

1
From the INSERM, UMR_S 1138, Teams 1 (R.U., A.F., S.E.M., F.J.) and 8 (N.V.), Centre de Recherche des Cordeliers, UPMC Univ Paris 06, Université Paris Descartes, Paris, France; Department of Medicine (DIMED), University of Padova, Padova, Italy (R.U., F.F.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (A.N.D.C., R.M.T.); Laboratory of Cardiovascular Endocrinology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Rome, Italy (A.F.); Department of Physiology and Institute of Biomedical Technologies, University of La Laguna, Tenerife, Spain (D.A.D.l.R.); Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (G.K.A.); Department of Nutrition, Nancy University Hospital, INSERM U954, Medical Faculty and CHU of Nancy, Vandoeuvre-les-Nancy, France (D.Q.); and INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, CHU de Nancy, and Université de Lorraine, and Investigation Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT) French Clinical Research Infrastructure Network (F-CRIN), Nancy, France (P.R., F.J.).
2
From the INSERM, UMR_S 1138, Teams 1 (R.U., A.F., S.E.M., F.J.) and 8 (N.V.), Centre de Recherche des Cordeliers, UPMC Univ Paris 06, Université Paris Descartes, Paris, France; Department of Medicine (DIMED), University of Padova, Padova, Italy (R.U., F.F.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (A.N.D.C., R.M.T.); Laboratory of Cardiovascular Endocrinology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Rome, Italy (A.F.); Department of Physiology and Institute of Biomedical Technologies, University of La Laguna, Tenerife, Spain (D.A.D.l.R.); Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (G.K.A.); Department of Nutrition, Nancy University Hospital, INSERM U954, Medical Faculty and CHU of Nancy, Vandoeuvre-les-Nancy, France (D.Q.); and INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, CHU de Nancy, and Université de Lorraine, and Investigation Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT) French Clinical Research Infrastructure Network (F-CRIN), Nancy, France (P.R., F.J.). frederic.jaisser@inserm.fr.

Abstract

Metabolic syndrome is a major risk factor for the development of diabetes mellitus and cardiovascular diseases. Pharmacological antagonism of the mineralocorticoid receptor (MR), a ligand-activated transcription factor, limits metabolic syndrome in preclinical models, but mechanistic studies are lacking to delineate the role of MR activation in adipose tissue. In this study, we report that MR expression is increased in visceral adipose tissue in a preclinical mouse model of metabolic syndrome and in obese patients. In vivo conditional upregulation of MR in mouse adipocytes led to increased weight and fat mass, insulin resistance, and metabolic syndrome features without affecting blood pressure. We identified prostaglandin D2 synthase as a novel MR target gene in adipocytes and AT56, a specific inhibitor of prostaglandin D2 synthase enzymatic activity, blunted adipogenic aldosterone effects. Moreover, translational studies showed that expression of MR and prostaglandin D2 synthase is strongly correlated in adipose tissues from obese patients.

KEYWORDS:

aldosterone; obesity; prostaglandin D2 synthase 21kDa, brain; spironolactone

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