title: Transactivation of Atg4b by C/EBPβ promotes autophagy to facilitate adipogenesis.
abstract: 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 β (C/EBPβ), 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/EBPβ 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/EBPβ 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/EBPβ 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.
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.forename: Jia-Xin
authors.initials: JX
authors.lastname: Huang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Shui-Rong
authors.initials: SR
authors.lastname: Zhou
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Qian
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Huang
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Dang
authors.forename: Qi-Qun
authors.initials: QQ
authors.lastname: Tang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D059748:Proteolysis; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D000071183:Autophagy-Related Proteins; D022782:CCAAT-Enhancer-Binding Protein-beta; C490981:Gtf2h1 protein, mouse; C498314:Klf2 protein, mouse; C529780:Klf3 protein, mouse; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; C582881:Atg4b protein, mouse; D003546:Cysteine Endopeptidases