Prostaglandins Promote and Block Adipogenesis through Opposing Effects on Peroxisome Proliferator-activated Receptor Î

• Published in: The Journal of biological chemistry Vol. 273; no. 4; p. 1855
• Main Authors: Mauricio J. Reginato, Samuel L. Krakow, Shannon T. Bailey, Mitchell A. Lazar
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 23.01.1998
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.4.1855

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 γ (PPARγ), a nuclear hormone receptor that is central to adipogenic determination. We report here that PGF2α blocks adipogenesis through activation of mitogen-activated protein kinase, resulting in inhibitory phosphorylation of PPARγ. Both mitogen-activated protein kinase activation and PPARγ phosphorylation are required for the anti-adipogenic effects of PGF2α. 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 PGF2α and PGJ2 signaling may thus be central to the development of obesity and diabetes.