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Rapid depot-specific activation of adipocyte precursor cells at the onset of obesity

Nature Cell Biology volume 17, pages 376385 (2015) | Download Citation

Abstract

Excessive accumulation of white adipose tissue (WAT) is the defining characteristic of obesity. WAT mass is composed primarily of mature adipocytes, which are generated through the proliferation and differentiation of adipocyte precursors (APs). Although the production of new adipocytes contributes to WAT growth in obesity, little is known about the cellular and molecular mechanisms underlying adipogenesis in vivo. Here, we show that high-fat diet feeding in mice rapidly and transiently induces proliferation of APs within WAT to produce new adipocytes. Importantly, the activation of adipogenesis is specific to the perigonadal visceral depot in male mice, consistent with the patterns of obesogenic WAT growth observed in humans. Furthermore, we find that in multiple models of obesity, the activation of APs is dependent on the phosphoinositide 3-kinase (PI3K)-AKT2 pathway; however, the development of WAT does not require AKT2. These data indicate that developmental and obesogenic adipogenesis are regulated through distinct molecular mechanisms.

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Acknowledgements

This work was supported by American Diabetes Association Award 7-12-JF-46, DERC pilot project grant DK045735 and NIDDK grant DK090489 to M.S.R., Lo Graduate Fellowship for Excellence in Stem Cell Research from the Yale Stem Cell Center to E.J., and EMBO long-term fellowship ALTF 132-2011 to C.D.C.

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Affiliations

  1. Department of Cell Biology, Yale University, Yale University School of Medicine, 375 Congress Ave New Haven, Connecticut 06520, USA

    • Elise Jeffery
  2. Section of Comparative Medicine, Yale University, Yale University School of Medicine, 375 Congress Ave New Haven, Connecticut 06520, USA

    • Christopher D. Church
    • , Laura Colman
    •  & Matthew S. Rodeheffer
  3. Department of Molecular, Cell and Developmental Biology, Yale University, Yale University School of Medicine, 375 Congress Ave New Haven, Connecticut 06520, USA

    • Brandon Holtrup
    •  & Matthew S. Rodeheffer
  4. Yale Stem Cell Center, Yale University, Yale University School of Medicine, 375 Congress Ave New Haven, Connecticut 06520, USA

    • Matthew S. Rodeheffer

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Contributions

E.J., C.D.C. and M.S.R. designed experiments. E.J., C.D.C., B.H., L.C. and M.S.R. performed experiments. E.J., C.D.C. and B.H. analysed data. E.J., C.D.C., B.H. and M.S.R. interpreted data. E.J. and M.S.R. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Matthew S. Rodeheffer.

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DOI

https://doi.org/10.1038/ncb3122

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