Adipocyte Mineralocorticoid Receptor Activation Leads to Metabolic Syndrome and Induction of Prostaglandin D2 Synthase.
Fiche publication
Date publication
juillet 2015
Journal
Hypertension (Dallas, Tex. : 1979)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ROSSIGNOL Patrick, Pr QUILLIOT Didier
Tous les auteurs :
Urbanet R, Nguyen Dinh Cat A, Feraco A, Venteclef N, El Mogrhabi S, Sierra-Ramos C, Alvarez de la Rosa D, Adler GK, Quilliot D, Rossignol P, Fallo F, Touyz RM, Jaisser F
Lien Pubmed
Résumé
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.
Mots clés
3T3-L1 Cells, Adipocytes, White, Aldosterone, pharmacology, Animals, Cell Line, Tumor, Dibenzocycloheptenes, pharmacology, Enzyme Induction, drug effects, Humans, Insulin Resistance, Intra-Abdominal Fat, metabolism, Intramolecular Oxidoreductases, biosynthesis, Lipocalins, biosynthesis, Male, Metabolic Syndrome, drug therapy, Mice, Mice, Obese, Mice, Transgenic, Mineralocorticoid Receptor Antagonists, pharmacology, Obesity, genetics, Piperidines, pharmacology, RNA, Messenger, biosynthesis, Receptors, Leptin, deficiency, Receptors, Mineralocorticoid, biosynthesis, Spironolactone, pharmacology, Subcutaneous Fat, metabolism, Up-Regulation
Référence
Hypertension. 2015 Jul;66(1):149-57