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

Hye Jin Kim, Hyunjii Cho, Ryan Alexander, Heide Christine Patterson, Minxia Gu, Kinyui Alice Lo, Dan Xu, Vera J. Goh, Long N. Nguyen, Xiaoran Chai, Cher X. Huang, Jean Paul Kovalik, Sujoy Ghosh, Mirko Trajkovski, David L. Silver, Harvey Lodish, Lei Sun

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


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 aswell as in the differentiation of brown adipocytes.

Original languageEnglish (US)
Pages (from-to)4045-4056
Number of pages12
Issue number12
StatePublished - Dec 1 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 by the American Diabetes Association.


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