Prostaglandins promote and block adipogenesis through opposing effects on peroxisome proliferator-activated receptor gamma

Fat cell differentiation is a critical aspect of obesity and diabetes. Dietary fatty acids are converted to arachidonic acid, which serves as precursor of prostaglandins (PGs). PGJ2 derivatives function as activating ligands for peroxisome proliferator-activated receptor gamma (PPAR gamma), a nuclear hormone receptor that is central to adipogenic determination. We report here that PGF2 alpha blocks adipogenesis through activation of mitogen-activated protein kinase, resulting in inhibitory phosphorylation of PPAR gamma. Both mitogen-activated protein kinase activation and PPAR gamma phosphorylation are required for the anti-adipogenic effects of PGF2 alpha. Thus, PG signals generated at a cell surface receptor regulate the program of gene expression required for adipogenesis by modulating the activity of a nuclear hormone receptor that is directly activated by other PG signals. The balance between PGF2 alpha and PGJ2 signaling may thus be central to the development of obesity and diabetes.