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

Y Oishi, I Manabe, K Tobe, K Tsushima, T Shindo… - Cell metabolism, 2005 - cell.com
Y Oishi, I Manabe, K Tobe, K Tsushima, T Shindo, K Fujiu, G Nishimura, K Maemura…
Cell metabolism, 2005cell.com
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 PPARγ 2. Constitutive overexpression of dominant-negative KLF5 inhibited …
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.
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