期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：26
页码：11817-11822
DOI：10.1073/pnas.0913367107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Adipose tissue controls body lipid and energy metabolism, as well as food intake, and abnormalities in adipose function play a central role in diseases such as obesity and type-2 diabetes. Adipocyte differentiation is controlled by a transcriptional cascade involving PPAR{gamma} and members of the C/EBP family of transcription factors. Here, we demonstrate that C/EBP{alpha} is targeted for degradation by the ubiquitin ligase Fbxw7 in a phosphorylation-dependent manner. Importantly, inactivation of Fbxw7 is sufficient to convert mouse preadipocytes into mature adipocytes in a manner dependent on C/EBP{alpha}. In addition, inactivation of Fbxw7 promotes adipocyte differentiation of human adult stem cells. Taken together, our results suggest that Fbxw7 is a negative regulator of adipogenesis by targeting C/EBP{alpha} for degradation. This notion is supported by the observation that the expression of Fbxw7 is down-regulated during adipocyte differentiation, resulting in the accumulation of proadipogenic proteins such as C/EBP{alpha}. Thus, Fbxw7 could be an important regulator of energy and lipid metabolism.
