Prostaglandins as PPARγ Modulators in Adipogenesis

Abstract

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. PPARγ 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 PPARγ function in adipocytes. Prostacyclin promotes the differentiation of adipocyte-precursor cells to adipose cells via activation of the expression of C/EBPβ and δ. These proteins are important transcription factors in the activation of the early phase of adipogenesis, and they activate the expression of PPARγ, which event precedes the maturation of adipocytes. PGE(2) and PGF(2α) 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 PPARγ. In contrast, PGD(2) and its non-enzymatic metabolite, Δ(12)-PGJ(2), activate the middle-late phase of adipocyte differentiation through both DP2 receptors and PPARγ. This paper focuses on potential roles of PGs as PPARγ modulators in adipogenesis and regulators of obesity.

Figure 1

Biosynthetic pathway of prostaglandins. PGJ₂, Δ¹²-PGJ₂, and 15d-PGJ₂ are converted from PGD₂ by nonenzymatic dehydrations.

Figure 2

Regulation of adipogenesis by prostaglandins. “Pre” indicates adipocyte precursor cells. “Early,” “Middle,” and “Late” mean early, middle, and late phases of adipogenesis, respectively.