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

Yumiko Oishi; Ichiro Manabe; Kazuyuki Tobe; Kensuke Tsushima; Takayuki Shindo; Katsuhito Fujiu; Go Nishimura; Koji Maemura; Toshimasa Yamauchi; Naoto Kubota; Ryo Suzuki; Toshio Kitamura; Shizuo Akira; Takashi Kadowaki; Ryozo Nagai

doi:10.1016/j.cmet.2004.11.005

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.

Authors

Yumiko Oishi¹, Ichiro Manabe, Kazuyuki Tobe, Kensuke Tsushima, Takayuki Shindo, Katsuhito Fujiu, Go Nishimura, Koji Maemura, Toshimasa Yamauchi, Naoto Kubota, Ryo Suzuki, Toshio Kitamura, Shizuo Akira, Takashi Kadowaki, Ryozo Nagai

Affiliation

¹ Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.

PMID: 16054042
DOI: 10.1016/j.cmet.2004.11.005

Abstract

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

Substances

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