KSRP ablation enhances brown fat gene program in white adipose tissue through reduced miR-150 expression

Academic Article

Abstract

  • Brown adipose tissue oxidizes chemical energy for heat generation and energy expenditure. Promoting brownlike transformation in white adipose tissue (WAT) is a promising strategy for combating obesity. Here, we find that targeted deletion of KH-type splicing regulatory protein (KSRP), an RNA-binding protein that regulates gene expression at multiple levels, causes a reduction in body adiposity. The expression of brown fat-selective genes is increased in subcutaneous/inguinal WAT (iWAT) of Ksrp-/- mice because of the elevated expression of PR domain containing 16 and peroxisome proliferator- activated receptor gamma coactivator 1a, which are key regulators promoting the brown fat gene program. The expression of microRNA (miR)-150 in iWAT is decreased due to impaired primary miR-150 processing in the absence of KSRP. We show that miR-150 directly targets and represses Prdm16 and Ppargc1a, and that forced expression of miR-150 attenuates the elevated expression of brown fat genes caused by KSRP deletion. This study reveals the in vivo function of KSRP in controlling brown-like transformation of iWAT through posttranscriptional regulation of miR-150 expression. © 2014 by the American Diabetes Association.
  • Published In

  • Diabetes  Journal
  • Digital Object Identifier (doi)

    Author List

  • Chou CF; Lin YY; Wang HK; Zhu X; Giovarelli M; Briata P; Gherzi R; Garvey WT; Chen CY
  • Start Page

  • 2949
  • End Page

  • 2961
  • Volume

  • 63
  • Issue

  • 9