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Diabetes. 2014 Dec;63(12):4045-56. doi: 10.2337/db14-0466. Epub 2014 Jul 9.

MicroRNAs are required for the feature maintenance and differentiation of brown adipocytes.

Author information

  • 1Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
  • 2Whitehead Institute for Biomedical Research, Cambridge, MA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA.
  • 3Whitehead Institute for Biomedical Research, Cambridge, MA Department of Pathology, Brigham and Women's Hospital, Boston, MA.
  • 4Institute of Molecular and Cell Biology, Singapore.
  • 5University of Geneva, Medical Faculty, Department of Cell Physiology and Metabolism, Centre Médical Universitaire (CMU), Geneva, Switzerland.
  • 6Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore Institute of Molecular and Cell Biology, Singapore sun.lei@duke-nus.edu.sg.

Abstract

Brown adipose tissue (BAT) is specialized to burn lipids for heat generation as a natural defense against cold and obesity. Previous studies established microRNAs (miRNAs) as essential regulators of brown adipocyte differentiation, but whether miRNAs are required for the feature maintenance of mature brown adipocytes remains unknown. To address this question, we ablated Dgcr8, a key regulator of the miRNA biogenesis pathway, in mature brown as well as in white adipocytes. Adipose tissue-specific Dgcr8 knockout mice displayed enlarged but pale interscapular brown fat with decreased expression of genes characteristic of brown fat and were intolerant to cold exposure. Primary brown adipocyte cultures in vitro confirmed that miRNAs are required for marker gene expression in mature brown adipocytes. We also demonstrated that miRNAs are essential for the browning of subcutaneous white adipocytes in vitro and in vivo. Using this animal model, we performed miRNA expression profiling analysis and identified a set of BAT-specific miRNAs that are upregulated during brown adipocyte differentiation and enriched in brown fat compared with other organs. We identified miR-182 and miR-203 as new regulators of brown adipocyte development. Taken together, our study demonstrates an essential role of miRNAs in the maintenance as well as in the differentiation of brown adipocytes.

© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

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