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Mir193b–365 is essential for brown fat differentiation

Nature Cell Biology volume 13, pages 958965 (2011) | Download Citation

Abstract

Mammals have two principal types of fat. White adipose tissue primarily serves to store extra energy as triglycerides, whereas brown adipose tissue is specialized to burn lipids for heat generation and energy expenditure as a defence against cold and obesity1,2. Recent studies have demonstrated that brown adipocytes arise in vivo from a Myf5-positive, myoblastic progenitor by the action of Prdm16 (PR domain containing 16). Here, we identified a brown-fat-enriched miRNA cluster, MiR-193b–365, as a key regulator of brown fat development. Blocking miR-193b and/or miR-365 in primary brown preadipocytes markedly impaired brown adipocyte adipogenesis by enhancing Runx1t1 (runt-related transcription factor 1; translocated to, 1) expression, whereas myogenic markers were significantly induced. Forced expression of Mir193b and/or Mir365 in C2C12 myoblasts blocked the entire programme of myogenesis, and, in adipogenic conditions, miR-193b induced myoblasts to differentiate into brown adipocytes. Mir193b–365 was upregulated by Prdm16 partially through Pparα. Our results demonstrate that Mir193b–365 serves as an essential regulator for brown fat differentiation, in part by repressing myogenesis.

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Acknowledgements

This work is supported by NIH grants DK047618, DK 068348, DK076848 and 5P01 HL066105, grant C-382-641-001-091 from the Singapore–MIT Alliance (SMA) and a graduate fellowship from SMA. Thanks for intellectual support, materials and advice from members of the laboratories of Drs P. Seale, D. Bartel and C. Emerson, and from all members of the Lodish laboratory. Thanks to Rochford’s laboratory for their generous gifts of Runx1t1 plasmid.

Author information

Author notes

    • Lei Sun
    •  & Huangming Xie

    These authors contributed equally to this work

    • Huangming Xie

    Present address: Division of Newborn Medicine, Department of Medicine, Children’s Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA

Affiliations

  1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA

    • Lei Sun
    • , Huangming Xie
    • , Ryan Alexander
    • , Bingbing Yuan
    • , Shilpa M. Hattangadi
    • , Qingqing Liu
    •  & Harvey F. Lodish
  2. Computation and Systems Biology, Singapore-MIT Alliance, National University of Singapore, 4 Engineering Drive 3, Singapore 117576, Singapore

    • Huangming Xie
  3. Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA

    • Marcelo A. Mori
    •  & C. Ronald Kahn
  4. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Ryan Alexander
    •  & Harvey F. Lodish
  5. Department of Hematology, Boston Children’s Hospital, Boston, Massachusetts 02115, USA

    • Shilpa M. Hattangadi
  6. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Harvey F. Lodish

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Contributions

L.S., H.X. and H.F.L. conceived the project and designed the experiments. L.S., H.X., M.A.M., R.A., B.Y., S.M.H. and Q.L. carried out the experiments. All authors analysed data. L.S., H.X., M.A.M. and H.F.L. wrote the manuscript. C.R.K. and H.F.L. supervised the project.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Harvey F. Lodish.

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DOI

https://doi.org/10.1038/ncb2286

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