miR17-92 cluster drives white adipose tissue browning

in Journal of Molecular Endocrinology
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  • 1 Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
  • 2 The University of the Chinese Academy of Sciences, Beijing, China
  • 3 Center for Advanced Biomedical Imaging and Photonics, Beth Israel Deaconess Medical Center, Harvard University, Boston, Massachusetts, USA
  • 4 Institute of Neuroscience and Translational Medicine, College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, China

Correspondence should be addressed to X Liu or W Jin: lxmxm_99@126.com or jinw@ioz.ac.cn
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White adipose tissue (WAT) browning may have beneficial effects for treating metabolic syndrome. miRNA are important regulators of the differentiation, development, and function of brown and beige adipocytes. Here, we found that the cold-inducible miRNA17-92 cluster is enriched in brown adipose tissue (BAT) compared with WAT. Overexpression of the miR17-92 cluster in C3H10T1/2 cells, a mouse mesenchymal stem cell line, enhanced the thermogenic capacity of adipocytes. Furthermore, we observed a significant reduction in adiposity in adipose tissue-specific miR17-92 cluster transgenic (TG) mice. This finding is partly explained by dramatic increases in white fat browning and energy expenditure. Interestingly, the miR17-92 cluster stimulated WAT browning without altering BAT activity in mice. In addition, when we removed the intrascapular BAT (iBAT), the TG mice could maintain their body temperature well under cold exposure. At the molecular level, we found that the miR17-92 cluster targets Rb1, a beige cell repressor in WAT. The present study reveals a critical role for the miR17-92 cluster in regulating WAT browning. These results may be helpful for better understanding the function of beige fat, which could compensate for the lack of BAT in humans, and may open new avenues for combatting metabolic syndrome.

Supplementary Materials

    • Supplementary Figure 1. Overexpression of the miR17-92 cluster improved the thermogenic function of 3T3L1 cells after brown differentiation. 3T3L1 cells were infected with miR17-92 cluster lentivirus, and then harvested on day 6 after brown adipocyte differentiation. A) Oil Red O staining. B) Western blots of Ucp1 and OXPHOS (n=3). C) The expression level of miR17-92 cluster (n=4). D) The expression of some thermogenic genes (n=4). Data are presented as means&#x00B1;SEM. *, p<0.05, **, p<0.01, and ***, p<0.001 compared with the control.
    • Supplementary Figure 2. The phenotype of miR17-92 cluster TG mice. A) Expression level of miR17-92 cluster in muscle (n=9-10). B) Expression level of miR17-92 cluster in serum (n=9-11). C) The glucose homeostasis of miR17-92 TG mice (n=9-11). D) Rectal temperature after 4 hrs of 4 &#x2103; cold exposure (n=9-11). Data are presented as means&#x00B1;SEM. *, p<0.05, **, p<0.01, and ***, p<0.001 compared with the control.
    • Supplementary Figure 3. The phenotype of iBAT minus miR17-92 cluster TG mice. A-B) The glucose homeostasis and physical activity of miR17-92 TG mice (n=11-12). C-D) The content of TG and glycerol levels in plasma after cold exposure of miR17-92 TG mice (n=11-12).
    • Supplementary Figure 4. The miR17-92 cluster directly targeted the Rb1 3&#x2019;-UTR. A) The expression level of UCP1 in BAT and Sub fat after cold stimulate in mice (n=6). B-D) The expression of potential miR17-92 target genes in the three adipose tissues (n=4-7). Data are presented as means&#x00B1;SEM. *, p<0.05, **, p<0.01, and ***, p<0.001 compared with the control.
    • Supplementary Table 1. Serological analysis of serum lipid levels in miR17-92 cluster TG mice.

 

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