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Publication : FTO influences adipogenesis by regulating mitotic clonal expansion.

First Author  Merkestein M Year  2015
Journal  Nat Commun Volume  6
Pages  6792 PubMed ID  25881961
Mgi Jnum  J:222710 Mgi Id  MGI:5645415
Doi  10.1038/ncomms7792 Citation  Merkestein M, et al. (2015) FTO influences adipogenesis by regulating mitotic clonal expansion. Nat Commun 6:6792
abstractText  The fat mass and obesity-associated (FTO) gene plays a pivotal role in regulating body weight and fat mass; however, the underlying mechanisms are poorly understood. Here we show that primary adipocytes and mouse embryonic fibroblasts (MEFs) derived from FTO overexpression (FTO-4) mice exhibit increased potential for adipogenic differentiation, while MEFs derived from FTO knockout (FTO-KO) mice show reduced adipogenesis. As predicted from these findings, fat pads from FTO-4 mice fed a high-fat diet show more numerous adipocytes. FTO influences adipogenesis by regulating events early in adipogenesis, during the process of mitotic clonal expansion. The effect of FTO on adipogenesis appears to be mediated via enhanced expression of the pro-adipogenic short isoform of RUNX1T1, which enhanced adipocyte proliferation, and is increased in FTO-4 MEFs and reduced in FTO-KO MEFs. Our findings provide novel mechanistic insight into how upregulation of FTO leads to obesity.
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