Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor

Peroxisome proliferator-activated receptor γ2 (PPARγ2) is an adipocyte-specific nuclear hormone receptor that has recently been identified as a key regulator of two fat cell enhancers. Transcriptional activation by PPARγ2 is potentiated by a variety of lipids and lipid-like compounds, including naturally occurring polyunsaturated fatty acids. We demonstrate here that retroviral expression of PPARγ2 stimulates adipose differentiation of cultured fibroblasts. PPAR activators promote the differentiation of PPARγ2-expressing cells in a dose-dependent manner. , a second transcription factor induced during adipocyte differentiation, can cooperate with PPARγ2 to stimulate the adipocyte program dramatically. Our results suggest that the physiologic role of PPARγ2 is to regulate development of the adipose lineage in response to endogenous lipid activators and that this factor may serve to link the process of adipocyte differentiation to systemic lipid metabolism.