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

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• 作者：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
• 刊名：Cell Metabolism
• 出版年：2005
• 出版时间：January 2005
• 年：2005
• 卷：1
• 期：1
• 页码：27-39
• 全文大小：833 K

文摘

Summary

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 PPARγ₂. 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/EBPβ and δ. KLF5, in turn, acts in concert with C/EBPβ/δ to activate the PPARγ₂ promoter. This study establishes KLF5 as a key component of the transcription factor network controlling adipocyte differentiation.