Transactivation of Atg4b by C/EBPβ Promotes Autophagy To Facilitate Adipogenesis
Transactivation of Atg4b by C/EBPβ Promotes Autophagy To Facilitate Adipogenesis
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DOI：
10.1128/mcb.00193-13
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发表时间：
2013-08-01
影响因子：
5.3
通讯作者：
Tang, Qi-Qun
中科院分区：
文献类型：
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作者：
Guo, Liang;Huang, Jia-Xin;Tang, Qi-Qun
自噬是一种高度保守的自我消化途径，参与多种生理和病理生理过程。最近的研究表明自噬在脂肪细胞分化中起着关键作用，但其作用的分子机制以及在此过程中如何调控尚不清楚。在这里，我们表明，CCAAT/增强子结合蛋白β（C/EBP β），一个重要的脂肪形成因子，是需要在3 T3-L1脂肪细胞分化过程中激活自噬。自噬相关基因Atg 4 b被鉴定为C/EBP β的从头靶基因，并显示在3 T3-L1脂肪细胞分化中起重要作用。此外，Klf 2和Klf 3的降解需要自噬，Klf 2和Klf 3是脂肪细胞分化的两种负调节剂，其由衔接蛋白p62/SQSTM 1介导。重要的是，在小鼠模型中进一步证实了C/EBP β对自噬的调节以及自噬在Klf 2/3降解和脂肪形成中的作用。我们的数据描述了C/EBP β在调节自噬中的新功能，并揭示了脂肪细胞分化过程中自噬的机制。这些对脂肪组织发育的分子机制的新见解提供了一种具有治疗肥胖及其相关代谢紊乱潜力的功能途径。
Autophagy is a highly conserved self-digestion pathway involved in various physiological and pathophysiological processes. Recent studies have implicated a pivotal role of autophagy in adipocyte differentiation, but the molecular mechanism for its role and how it is regulated during this process are not clear. Here, we show that CCAAT/enhancer-binding protein beta (C/EBP beta), an important adipogenic factor, is required for the activation of autophagy during 3T3-L1 adipocyte differentiation. An autophagy-related gene, Atg4b, is identified as a de novo target gene of C/EBP beta and is shown to play an important role in 3T3-L1 adipocyte differentiation. Furthermore, autophagy is required for the degradation of Klf2 and Klf3, two negative regulators of adipocyte differentiation, which is mediated by the adaptor protein p62/SQSTM1. Importantly, the regulation of autophagy by C/EBP beta and the role of autophagy in Klf2/3 degradation and in adipogenesis are further confirmed in mouse models. Our data describe a novel function of C/EBP beta in regulating autophagy and reveal the mechanism of autophagy during adipocyte differentiation. These new insights into the molecular mechanism of adipose tissue development provide a functional pathway with therapeutic potential against obesity and its related metabolic disorders.