Cdk4 promotes adipogenesis through PPARgamma activation. Cell Metab

Cell cycle regulators, such as E2F1 and Retinoblastoma (RB) play crucial roles in the control of adipogenesis, mostly through the control of the transition between preadipocyte proliferation and adipocyte differentiation. Cyclin-dependent kinase 4 (cdk4) is a serine/threonine kinase that works in complex with D-type cyclins to phosphorylate RB mediating the commitment of the cells to enter cell cycle in response to external stimuli. Since cdk4 is an upstream regulator of the E2F-RB pathway we hypothesized that cdk4 is a good target for new factors that regulate adipogenesis. In this study we found that cdk4 inhibition impairs adipocyte differentiation and function. Disruption of cdk4 or activating mutations in cdk4 in primary mouse embryonic fibroblast, results in reduced and increased adipogenic potential respectively of these cells. We show that the effects of cdk4 are not limited to the control of differentiation but cdk4 also participates in adipocyte function through activation of PPARγ. H AL author