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 journalArticle

68 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1003626
JournalPLoS Genetics
Volume9
Issue number7
DOIs
StatePublished - Jul 2013

Fingerprint

White Adipose Tissue
white adipose tissue
Subcutaneous Fat
adipocytes
Adipocytes
Brown Adipose Tissue
brown adipose tissue
mice
Genes
Up-Regulation
genes
gene
Adipogenesis
3' Untranslated Regions
3' untranslated regions
glucose tolerance
MicroRNAs
microRNA
insulin resistance
skeletal muscle

ASJC Scopus subject areas

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

Cite this

Liu, W., Bi, P., Shan, T., Yang, X., Yin, H., Wang, Y. X., ... Kuang, S. (2013). miR-133a Regulates Adipocyte Browning In Vivo. PLoS Genetics, 9(7), [e1003626]. https://doi.org/10.1371/journal.pgen.1003626

miR-133a Regulates Adipocyte Browning In Vivo. / Liu, Weiyi; Bi, Pengpeng; Shan, Tizhong; Yang, Xin; Yin, Hang; Wang, Yong Xu; Liu, Ning; Rudnicki, Michael A.; Kuang, Shihuan.

In: PLoS Genetics, Vol. 9, No. 7, e1003626, 07.2013.

Research output: Contribution to journalArticle

Liu, W, Bi, P, Shan, T, Yang, X, Yin, H, Wang, YX, Liu, N, Rudnicki, MA & Kuang, S 2013, 'miR-133a Regulates Adipocyte Browning In Vivo', PLoS Genetics, vol. 9, no. 7, e1003626. https://doi.org/10.1371/journal.pgen.1003626
Liu W, Bi P, Shan T, Yang X, Yin H, Wang YX et al. miR-133a Regulates Adipocyte Browning In Vivo. PLoS Genetics. 2013 Jul;9(7). e1003626. https://doi.org/10.1371/journal.pgen.1003626
Liu, Weiyi ; Bi, Pengpeng ; Shan, Tizhong ; Yang, Xin ; Yin, Hang ; Wang, Yong Xu ; Liu, Ning ; Rudnicki, Michael A. ; Kuang, Shihuan. / miR-133a Regulates Adipocyte Browning In Vivo. In: PLoS Genetics. 2013 ; Vol. 9, No. 7.
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