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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Brown / metabolism*
  • Adipocytes, White / metabolism
  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Gene Knockout Techniques
  • Mice
  • Mice, Knockout
  • MicroRNAs / physiology*
  • RNA, Messenger / analysis*
  • RNA-Binding Proteins / genetics

Substances

  • Dgcr8 protein, mouse
  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins