miR-133a Regulates Adipocyte Browning In Vivo

Weiyi Liu, Pengpeng Bi, Tizhong Shan, Xin Yang, Hang Yin, Yong Xu Wang, Ning Liu, Michael A. Rudnicki, Shihuan Kuang

Research output: Contribution to journalArticlepeer-review

107 Scopus citations


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.

Original languageEnglish (US)
Article numbere1003626
JournalPLoS genetics
Issue number7
StatePublished - Jul 2013

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research


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