MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice

Nat Commun. 2013;4:2883. doi: 10.1038/ncomms3883.

Abstract

MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports have indicated that miR-33, which is located within the intron of sterol regulatory element-binding protein (SREBP) 2, controls cholesterol homoeostasis and may be a potential therapeutic target for the treatment of atherosclerosis. Here we show that deletion of miR-33 results in marked worsening of high-fat diet-induced obesity and liver steatosis. Using miR-33(-/-)Srebf1(+/-) mice, we demonstrate that SREBP-1 is a target of miR-33 and that the mechanisms leading to obesity and liver steatosis in miR-33(-/-) mice involve enhanced expression of SREBP-1. These results elucidate a novel interaction between SREBP-1 and SREBP-2 mediated by miR-33 in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, High-Fat / adverse effects
  • Fatty Liver / genetics*
  • Fatty Liver / metabolism
  • Gene Expression Regulation*
  • Humans
  • Introns
  • Lipid Metabolism
  • Male
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Obesity / genetics*
  • Obesity / metabolism
  • Sterol Regulatory Element Binding Protein 1 / genetics*
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Sterol Regulatory Element Binding Protein 2 / genetics
  • Sterol Regulatory Element Binding Protein 2 / metabolism

Substances

  • MicroRNAs
  • Mirn33 microRNA, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Sterol Regulatory Element Binding Protein 2