title: Antiadipogenic effects of the mineralocorticoid receptor antagonist drospirenone: potential implications for the treatment of metabolic syndrome.
abstract: The mineralocorticoid receptor (MR) mediates aldosterone- and glucocorticoid-induced adipocyte differentiation. Drospirenone (DRSP) is a potent synthetic antimineralocorticoid with progestogenic and antiandrogenic properties, which is widely used for contraception and hormone replacement therapy. We investigated its potential role on adipocyte differentiation. The effects of DRSP were studied in murine preadipocyte cell lines and primary cultures of human preadipocytes. Differentiation markers and mechanisms underlying phenotypic variations in response to DRSP were explored. Early exposure to DRSP during differentiation led to a marked dose-dependent inhibition of adipose differentiation and triglyceride accumulation in 3T3-L1 and 3T3-F442A cells. DRSP also markedly inhibited adipose conversion of human primary preadipocytes derived from visceral (mesenteric and epicardial) and subcutaneous fat. This effect was MR-dependent and did not involve the glucocorticoid, androgen, or progesterone receptors. DRSP inhibited clonal expansion of preadipocytes and decreased expression of PPARγ, a key transcriptional mediator of adipogenesis, but had no effect on lipolysis, glucose uptake, and PPARγ binding to its ligands. DRSP exerts a potent antiadipogenic effect that is related to an alteration of the transcriptional control of adipogenesis via an antagonistic effect on the MR. Selective MR blockade therefore has promise as a novel therapeutic option for the control of excessive adipose tissue deposition and its related metabolic complications.
authors.affiliation: Centre for Clinical and Basic Research, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, 81-00163 Rome, Italy. massimiliano.caprio@sanraffaele.it
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Caprio
authors.forename: Antonella
authors.initials: A
authors.lastname: Antelmi
authors.forename: Gérard
authors.initials: G
authors.lastname: Chetrite
authors.forename: Adeline
authors.initials: A
authors.lastname: Muscat
authors.forename: Caterina
authors.initials: C
authors.lastname: Mammi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Marzolla
authors.forename: Andrea
authors.initials: A
authors.lastname: Fabbri
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Zennaro
authors.forename: Bruno
authors.initials: B
authors.lastname: Fève
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D000736:Androstenes / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D050356:Lipid Metabolism; D024821:Metabolic Syndrome / Q000188:drug therapy*; D051379:Mice; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology
chemical_list: D000736:Androstenes; D000451:Mineralocorticoid Receptor Antagonists; C035144:drospirenone