Functional role of RXRs and PPARγ in mature adipocytes

The peroxisome proliferator-activated receptor γ (PPARγ) is abundantly expressed in adipocytes, and plays an important role in adipocyte differentiation and fat accretion. It is a heterodimeric partner of the retinoid X receptors α, β and γ, which are also expressed in the adipose tissue. As lethality of PPARγ−/− and RXRα−/− mouse fetuses precluded the analysis of PPARγ and RXRα functions in mature adipocytes, we generated RXRαad−/− and PPARγad−/− mice, in which RXRα and PPARγ are selectively ablated in adult adipocytes, respectively. Even though the adiposity of RXRαad−/− mice is similar to that of control mice when fed a regular diet, they are resistant to chemically and dietary-induced obesity. However, mature adipocytes lacking either both RXRα and RXRγ or PPARγ die, and are replaced by newly formed adipocytes. Thus, in adipocytes, RXRα is essential for lipogenesis, but RXRγ can functionally replace RXRα for the adipocyte vital functions exerted by PPARγ/RXR heterodimers.