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FTO influences adipogenesis by regulating mitotic clonal expansion

Merkestein, M., Laber, S., McMurray, F., Andrew, D., Gregor, S., Sanderson, J., Li, M., Usher, S., Sellayah, D., Ashcroft, F. M. and Cox, R. D. (2015) FTO influences adipogenesis by regulating mitotic clonal expansion. Nature Communications, 6. 6792. ISSN 2041-1723

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To link to this item DOI: 10.1038/ncomms7792

Abstract/Summary

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.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:43343
Publisher:Nature Publishing Group

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