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

KLF8 (Kruppel-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 gamma (PPAR gamma) and CCAAT/enhancer-binding protein alpha (C/EBP alpha). 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 PPAR gamma 2 and C/EBP alpha promoter activity, suggesting that KLF8 is an upstream regulator of PPAR gamma and C/EBP alpha. The KLF8 binding sites were localized by site mutation analysis to -191 region in C/EBP alpha promoter and -303 region in PPAR gamma promoter, respectively. Taken together, these data reveal that KLF8 is a key component of the transcription factor network that controls terminal differentiation during adipogenesis.