MicroRNAs are required for the feature maintenance and differentiation of brown adipocytes
- Hye-Jin Kim1,
- Hyunjii Cho3,4,
- Ryan Alexander3,4,
- Heide Christine Patterson3,5,
- Minxia Gu1,
- Kinyui Alice Lo2,
- Dan Xu1,
- Vera J. Goh1,
- Long N. Nguyen1,
- Xiaoran Chai1,
- Cher X. Huang3,4,
- Jean-Paul Kovalik1,
- Sujoy Ghosh1,
- Mirko Trajkovski6,
- David L. Silver1,
- Harvey Lodish3,4 and
- Lei Sun1,2,*
- 1Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, 8 College Road, 169857, Singapore
- 2Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore
- 3Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
- 4Department of Biology, Massachusetts Institute of Technology,
- 5Department of Pathology, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA
- 6University of Geneva, Medical Faculty, Department of Cell Physiology and Metabolism, Centre Médical Universitaire (CMU), 1211 Geneva 4, Switzerland
- *Corresponding Author:
Brown adipose tissue is specialized to burn lipids for heat generation as a natural defense against cold and obesity. Previous studies established microRNAs as essential regulators of brown adipocyte differentiation, but it remains unknown whether microRNAs are required for the feature maintenance of mature brown adipocytes. To address this question, we ablated Dgcr8, a key regulator of the microRNA biogenesis pathway, in mature brown as well as white adipocytes. The adipose tissue -specific Dgcr8 knockout mice displayed enlarged but pale interscapular brown fat with decreased expression of genes characteristic of brown fat, and the mice were intolerant to cold exposure. In vitro primary brown adipocyte cultures confirmed that microRNAs are required for marker gene expression in mature brown adipocytes. We also demonstrated that microRNAs are essential for the browning of subcutaneous white adipocyte both in vitro and in vivo. Using this animal model, we performed microRNA expression profiling analysis and identified a set of BAT-specific microRNAs that are up-regulated during brown adipocyte differentiation and enriched in brown fat compared to 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 microRNAs in the maintenance as well as the differentiation of brown adipocytes.
- Received March 21, 2014.
- Accepted July 2, 2014.
- © 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. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.