RESEARCH ARTICLE Cyclin Y Is Involved in the Regulation of Adipogenesis and Lipid

A newmember of the cyclin family cyclin Y (CCNY) is involved in the regulation of various physiological processes. In this study, the role of CCNY in energy metabolism was charac-terized. We found that compared with wild-type (WT) mice, Ccny knockout (KO) mice had both lower body weight and lower fat content. The Ccny KOmice also had a higher meta-bolic rate, resisted the stress of a high-fat diet, and were sensitive to calorie restriction. The expression levels of UCP1 and PGC1α were significantly higher in the brown adipose tissue (BAT) of the Ccny KOmice than that of the WT littermate controls, whereas there was no significant difference in BAT weight between the WT and the Ccny KOmice. In addition, the down-regulation of Ccny resulted in suppression of white adipocyte differentiation both in vivo and in vitro, while the expression of Ccnywas up-regulated by C/EBPα. Furthermore, both hepatocytes and HepG2 cells that were depleted of Ccnywere insensitive to insulin stimulation, consistent with the significant inhibition of insulin sensitivity in the liver of the Ccny KOmice, but no significant changes in WAT and muscle, indicating that CCNY is involved in regulating the hepatic insulin signaling pathway. The hepatic insulin resistance generated by Ccny depletion resulted in down-regulation of the sterol-regulatory element-binding protein (SREBP1) and fatty acid synthase (FASN). Together, these results provide a new link between CCNY and lipid metabolism in mice, and suggest that inhibition of CCNYmay offer a therapeutic approach to obesity and diabetes