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FTO influences adipogenesis by regulating mitotic clonal expansion

Author

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  • Myrte Merkestein

    (MRC Harwell, Mammalian Genetics Unit
    Anatomy and Genetics, University of Oxford)

  • Samantha Laber

    (MRC Harwell, Mammalian Genetics Unit
    Anatomy and Genetics, University of Oxford)

  • Fiona McMurray

    (MRC Harwell, Mammalian Genetics Unit)

  • Daniel Andrew

    (MRC Harwell, Mammalian Genetics Unit)

  • Gregor Sachse

    (Anatomy and Genetics, University of Oxford)

  • Jeremy Sanderson

    (MRC Harwell, Mammalian Genetics Unit)

  • Mengdi Li

    (MRC Harwell, Mammalian Genetics Unit)

  • Samuel Usher

    (Anatomy and Genetics, University of Oxford)

  • Dyan Sellayah

    (MRC Harwell, Mammalian Genetics Unit
    Anatomy and Genetics, University of Oxford)

  • Frances M. Ashcroft

    (Anatomy and Genetics, University of Oxford)

  • Roger D. Cox

    (MRC Harwell, Mammalian Genetics Unit)

Abstract

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.

Suggested Citation

  • Myrte Merkestein & Samantha Laber & Fiona McMurray & Daniel Andrew & Gregor Sachse & Jeremy Sanderson & Mengdi Li & Samuel Usher & Dyan Sellayah & Frances M. Ashcroft & Roger D. Cox, 2015. "FTO influences adipogenesis by regulating mitotic clonal expansion," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7792
    DOI: 10.1038/ncomms7792
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