title: miR-133a regulates adipocyte browning in vivo.
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.
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Liu
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Bi
authors.forename: Tizhong
authors.initials: T
authors.lastname: Shan
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
authors.forename: Yong-Xu
authors.initials: YX
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rudnicki
authors.forename: Shihuan
authors.initials: S
authors.lastname: Kuang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D022722:Thermogenesis / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; C521133:Prdm16 protein, mouse; D014157:Transcription Factors