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.
Date of this Version
7-11-2013
DOI
10.1371/journal.pgen.1003626
Recommended Citation
Liu, Weiyi; Bi, Pengpeng; Shan, Tizhong; Yang, Xin; Yin, Hang; Wang, Yong-Xu; Liu, Ning; Rudnicki, Michael A.; and Kuang, Shihuan, "miR-133a Regulates Adipocyte Browning In Vivo." (2013). School of Aeronautics and Astronautics Faculty Publications. Paper 1.
http://dx.doi.org/10.1371/journal.pgen.1003626
Comments
This is the publisher pdf of Liu W, Bi P, Shan T, Yang X, Yin H, et al. (2013) miR-133a Regulates Adipocyte Browning In Vivo. PLoS Genet 9(7): e1003626 and is available at: 10.1371/journal.pgen.1003626.