Adipose tissue and bone: role of PPAR gamma in adipogenesis and osteogenesis

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a critical factor for the reciprocal regulation of adipogenesis and osteogenesis. Because of their insulin-sensitizing effect, PPAR gamma agonists, the thiazolidinediones (TZDs), have been widely used for the treatment of type 2 diabetes mellitus; however, the use of TZDs has also been revealed to cause bone loss and bone fractures. The nodal point of regulation of skeletal metabolism by PPAR gamma activation may reside in its role in cell fate determination of mesenchymal stem cells toward adipogenesis at the expense of osteogenesis. In addition, accumulating evidence demonstrates that PPAR gamma possesses a circadian expression profile and plays an important role in the skeletal and adipose metabolism regulated by the circadian clock network. Recently, we have shown that nocturnin, a circadian-regulated gene, enhances PPAR gamma activity, resulting in the suppression of osteogenesis and enhancement of adipogenesis, thus providing additional evidence of the link between circadian networks and PPAR gamma. In this review, we will focus on the emerging concept of PPAR gamma as a regulator for skeletal metabolism and summarize recent findings about one of the mechanisms on how PPAR gamma is connected to the circadian-regulatory system, which involves nocturnin.