Abstract 1096: Krüppel-like Factor 6 is a Key Transcription Factor in Adipocyte Differentiation
Introduction: Obesity and metabolic syndrome are regarded as major risk factors for cardiovascular disease. Krüppel-like zinc-finger transcription factors (KLFs) are important regulators of development, cellular differentiation and growth, and pathogenesis of atherosclerosis. Recent studies suggest a potential role for KLFs (e.g. KLF2, KLF4, KLF5 and KLF15) in adipogenesis. KLF6 is ubiquitously expressed and is also suggested to play an important role in adipogenesis. However, the precise mechanisms of its actions have yet to be addressed.
Methods&Results: In the present study, we investigated whether KLF6 is involved in adiposity. Expression of KLF6 in white adipose tissue was significantly increased in mice fed a high fat diet, whereas adipocytes from KLF6+/− mice were smaller and showed a reduced hypertrophic response to this dietary manipulation. KLF6+/− mice were resistant to high fat-induced obesity and glucose intolerance compared with wild-type littermate. Embryonic fibroblasts from KLF6+/− mice were impaired in adipogenic differentiation. In 3T3-L1 preadipocytes, KLF6 expression was induced in a biphasic pattern, at a very early and a late stage of differentiation. KLF6 silencing by siRNA at very early phases reduced mRNA levels of CCAAT element binding protein (C/EBP) beta and delta and inhibited adipocyte differentiation, but KLF6 silencing by siRNA at later phases was not involved in adipocyte differentiation. In contrast, overexpression of KLF6 induced adipocyte differentiation.
Conclusion: Our data suggested that KLF6 can drive adipocyte differentiation through indirect activation of C/EBP families at very early phases. Taken together, KLF6 is a key transcription factor in adipocyte differentiation and adiposity.