KSRP Ablation Enhances Brown Fat Gene Program in White Adipose Tissue through Reduced miR-150 Expression

  1. Ching-Yi Chen1,*
  1. 1Department of Biochemistry & Molecular Genetics
  2. 2Department of Nutrition Sciences University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
  3. 3Gene Expression Regulation Laboratory, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy
  1. *Corresponding Author: W. Timothy Garvey, E-mail: garveyt{at}uab.edu and Ching-Yi Chen, E-mail: cchen{at}uab.edu

Abstract

Brown adipose tissue (BAT) oxidizes chemical energy for heat generation and energy expenditure. Promoting brown-like transformation in white adipose tissue (WAT) is a promising strategy to combat 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. Expression of brown fat-selective genes is increased in subcutaneous/inguinal WAT (iWAT) of Ksrp-/- mice due to elevated expression of PRDM16 and PPARGC1α, key regulators promoting brown fat gene program. Expression of miR-150 in iWAT is decreased due to impaired pri-miR-150 processing in the absence of KSRP. We show that miR-150 directly targets and represses Prdm16 and Ppargc1a and 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 post-transcriptional regulation of miR-150 expression.

  • Received December 17, 2013.
  • Accepted April 3, 2014.

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