Krüppel-Like Factor KLF8 Plays a Critical Role in Adipocyte Differentiation

Abstract

KLF8 (Krüppel-like factor 8) is a zinc-finger transcription factor known to play an essential role in the regulation of the cell cycle, apoptosis, and differentiation. However, its physiological roles and functions in adipogenesis remain unclear. In the present study, we show that KLF8 acts as a key regulator controlling adipocyte differentiation. In 3T3-L1 preadipocytes, we found that KLF8 expression was induced during differentiation, which was followed by expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Adipocyte differentiation was significantly attenuated by the addition of siRNA against KLF8, whereas overexpression of KLF8 resulted in enhanced differentiation. Furthermore, luciferase reporter assays demonstrated that overexpression of KLF8 induced PPARγ2 and C/EBPα promoter activity, suggesting that KLF8 is an upstream regulator of PPARγ and C/EBPα. The KLF8 binding sites were localized by site mutation analysis to −191 region in C/EBPα promoter and −303 region in PPARγ promoter, respectively. Taken together, these data reveal that KLF8 is a key component of the transcription factor network that controls terminal differentiation during adipogenesis.

Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis

“…The initial link was provided by Gray and colleagues, who showed that KLF15 regulates glucose metabolism (51). Since then, 8 additional members of this gene family have been shown to regulate adipogenesis both in mammals and worms (52,53). Several KLF factors (e.g., KLF10, KLF11, KLF15) have been shown to regulate hepatic metabolism (22,(54)(55)(56).…”

G0/G1 switch gene 2 has a critical role in adipocyte differentiation

“…Real-time qPCR was performed using the SYBR Green Master mix in a total volume of 20 ml, as previously described. 28 Transcripts were detected by real-time qPCR with a Step One instrument (Applied Biosystems, Foster City, CA, USA). A standard curve was used to calculate mRNA level relative to that of a control gene, ribosomal L32.…”

Emerging roles of zinc finger proteins in regulating adipogenesis

“…Moreover, both KLF15 and KLF9 act synergistically with C/EBPα to increase the activity of the PPARγ gene promoter [85–87]. KLF4, KLF5, KLF6, and KLF8 expressions were induced at an early stage of differentiation [88–91]. Down-regulated expression of KLF5 inhibited adipocyte differentiation, whereas overexpression of KLF5 induced differentiation without hormonal stimulation [88].…”