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Mir193b–365 is essential for brown fat differentiation

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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Figure 1: Mir193b–365 is enriched in BAT.
Figure 2: Mir193b–365 is required for brown adipocyte adipogenesis.
Figure 3: Ectopic expression of miR-193b and/or miR-365 inhibits C2C12 myogenic differentiation.
Figure 4: Ectopic expression of miR-193b induces C2C12 to form brown adipocytes under adipogenic differentiation conditions.
Figure 5: Mir193b–365 is regulated by Prdm16.

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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.

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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.

Corresponding author

Correspondence to Harvey F. Lodish.

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Sun, L., Xie, H., Mori, M. et al. Mir193b–365 is essential for brown fat differentiation. Nat Cell Biol 13, 958–965 (2011). https://doi.org/10.1038/ncb2286

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