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- Title
miR-133a Regulates Adipocyte Browning In Vivo.
- Authors
Liu, Weiyi; Bi, Pengpeng; Shan, Tizhong; Yang, Xin; Yin, Hang; Wang, Yong-Xu; Liu, Ning; Rudnicki, Michael A.; Kuang, Shihuan
- Abstract
Prdm16 determines the bidirectional fate switch of skeletal muscle/brown adipose tissue (BAT) and regulates the thermogenic gene program of subcutaneous white adipose tissue (SAT) in mice. Here we show that miR-133a, a microRNA that is expressed in both BAT and SATs, directly targets the 3′ UTR of Prdm16. The expression of miR-133a dramatically decreases along the commitment and differentiation of brown preadipocytes, accompanied by the upregulation of Prdm16. Overexpression of miR-133a in BAT and SAT cells significantly inhibits, and conversely inhibition of miR-133a upregulates, Prdm16 and brown adipogenesis. More importantly, double knockout of miR-133a1 and miR-133a2 in mice leads to elevations of the brown and thermogenic gene programs in SAT. Even 75% deletion of miR-133a (a1−/−a2+/−) genes results in browning of SAT, manifested by the appearance of numerous multilocular UCP1-expressing adipocytes within SAT. Additionally, compared to wildtype mice, miR-133a1−/−a2+/− mice exhibit increased insulin sensitivity and glucose tolerance, and activate the thermogenic gene program more robustly upon cold exposure. These results together elucidate a crucial role of miR-133a in the regulation of adipocyte browning in vivo.
- Subjects
ADIPOSE tissues; INSULIN research; MICRORNA genetics; BODY temperature regulation; ADIPOGENESIS
- Publication
PLoS Genetics, 2013, Vol 9, Issue 7, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1003626