Distinct regulatory mechanisms governing embryonic versus adult adipocyte maturation

控制胚胎和成人脂肪细胞成熟的不同调节机制

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作者:Qiong A Wang, Caroline Tao, Lei Jiang, Mengle Shao, Risheng Ye, Yi Zhu, Ruth Gordillo, Aktar Ali, Yun Lian, William L Holland, Rana K Gupta, Philipp E Scherer

Abstract

Pathological expansion of adipose tissue contributes to the metabolic syndrome. Distinct depots develop at various times under different physiological conditions. The transcriptional cascade mediating adipogenesis is established in vitro, and centres around a core program involving PPARγ and C/EBPα. We developed an inducible, adipocyte-specific knockout system to probe the requirement of key adipogenic transcription factors at various stages of adipogenesis in vivo. C/EBPα is essential for all white adipogenic conditions in the adult stage, such as adipose tissue regeneration, adipogenesis in muscle and unhealthy expansion of white adipose tissue during high-fat feeding or due to leptin deficiency. Surprisingly, terminal embryonic adipogenesis is fully C/EBPα independent, but does however depend on PPARγ; cold-induced beige adipogenesis is also C/EBPα independent. Moreover, C/EBPα is not vital for adipocyte survival in the adult stage. We reveal a surprising diversity of transcriptional signals required at different stages of adipogenesis in vivo.

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