Krüppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation

Cell Metab. 2005 Jan;1(1):27-39. doi: 10.1016/j.cmet.2004.11.005.


Krüppel-like factor 5 (KLF5) is a zinc-finger transcription factor known to play a pivotal role in the pathogenesis of cardiovascular disease. Here, we show that neonatal heterozygous KLF5 knockout mice exhibit a marked deficiency in white adipose tissue development, suggesting that KLF5 is also required for adipogenesis. In 3T3-L1 preadipocytes, KLF5 expression was induced at an early stage of differentiation, and this was followed by expression of PPARgamma2. Constitutive overexpression of dominant-negative KLF5 inhibited adipocyte differentiation, whereas overexpression of wild-type KLF5 induced differentiation even without hormonal stimulation. Moreover, embryonic fibroblasts obtained from KLF5+/- mice showed much attenuated adipocyte differentiation, confirming the key role played by KLF5 in adipocyte differentiation. KLF5 expression is induced by C/EBPbeta and delta. KLF5, in turn, acts in concert with C/EBPbeta/delta to activate the PPARgamma2 promoter. This study establishes KLF5 as a key component of the transcription factor network controlling adipocyte differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Animals
  • Blotting, Western
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • CCAAT-Enhancer-Binding Protein-delta
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Differentiation
  • Chromatin / metabolism
  • Chromatin Immunoprecipitation
  • Fibroblasts / metabolism
  • Gene Expression Regulation*
  • Genes, Dominant
  • HeLa Cells
  • Heterozygote
  • Humans
  • Immunoprecipitation
  • Kruppel-Like Transcription Factors
  • Luciferases / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Genetic
  • Mutation
  • NIH 3T3 Cells
  • PPAR gamma / metabolism
  • Plasmids / metabolism
  • Promoter Regions, Genetic
  • RNA, Small Interfering / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription Factors / metabolism
  • Transfection


  • CCAAT-Enhancer-Binding Protein-beta
  • CCAAT-Enhancer-Binding Proteins
  • CEBPD protein, human
  • Cebpd protein, mouse
  • Chromatin
  • Klf5 protein, mouse
  • Kruppel-Like Transcription Factors
  • PPAR gamma
  • RNA, Small Interfering
  • Trans-Activators
  • Transcription Factors
  • CCAAT-Enhancer-Binding Protein-delta
  • Luciferases