Cdk4 promotes adipogenesis through PPARgamma activation

Cell Metab. 2005 Oct;2(4):239-49. doi: 10.1016/j.cmet.2005.09.003.


Cell cycle regulators such as E2F1 and retinoblastoma (RB) play crucial roles in the control of adipogenesis, mostly by controlling the transition between preadipocyte proliferation and adipocyte differentiation. The serine-threonine kinase cyclin-dependent kinase 4 (cdk4) works in a complex with D-type cyclins to phosphorylate RB, mediating the entry of cells into the cell cycle in response to external stimuli. Because cdk4 is an upstream regulator of the E2F-RB pathway, we tested whether cdk4 was a target for new factors that regulate adipogenesis. Here we find that cdk4 inhibition impairs adipocyte differentiation and function. Disruption of cdk4 or activating mutations in cdk4 in primary mouse embryonic fibroblasts 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; cdk4 also participates in adipocyte function through activation of PPARgamma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Adipogenesis / drug effects
  • Adipogenesis / physiology*
  • Animals
  • Biological Transport
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism*
  • Gene Expression Regulation
  • Genes, Reporter / genetics
  • Glucose / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • PPAR gamma / metabolism*
  • Protein Binding
  • Protein Transport
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transfection


  • PPAR gamma
  • RNA, Messenger
  • Cdk4 protein, mouse
  • Cyclin-Dependent Kinase 4
  • Glucose