Prostaglandins as PPARγ Modulators in Adipogenesis

Adipocytes and fat cells play critical roles in the regulation of energy homeostasis. Adipogenesis (adipocyte differentiation) is regulated via a complex process including coordinated changes in hormone sensitivity and gene expression. PPAR. is a ligand-dependent transcription factor and important in adipogenesis, as it enhances the expression of numerous adipogenic and lipogenic genes in adipocytes. Prostaglandins (PGs), which are lipid mediators, are associated with the regulation of PPAR. function in adipocytes. Prostacyclin promotes the differentiation of adipocyte-precursor cells to adipose cells via activation of the expression of C/EBP beta and delta. These proteins are important transcription factors in the activation of the early phase of adipogenesis, and they activate the expression of PPAR., which event precedes the maturation of adipocytes. PGE(2) and PGF(2 alpha) strongly suppress the early phase of adipocyte differentiation by enhancing their own production via receptor-mediated elevation of the expression of cycloxygenase-2, and they also suppress the function of PPAR gamma. In contrast, PGD(2) and its non-enzymatic metabolite, Delta(12)-PGJ(2), activate themiddle-late phase of adipocyte differentiation through both DP2 receptors and PPAR gamma. This paper focuses on potential roles of PGs as PPAR gamma modulators in adipogenesis and regulators of obesity.