KSRP Ablation Enhances Brown Fat Gene Program in White Adipose Tissue Through Reduced miR-150 Expression
- Chu-Fang Chou1,
- Yi-Yu Lin1,
- Hsu-Kun Wang1,
- Xiaolin Zhu2,
- Matteo Giovarelli3,
- Paola Briata3,
- Roberto Gherzi3,
- W. Timothy Garvey2⇑ and
- Ching-Yi Chen1⇑
- 1Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL
- 2Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL
- 3Gene Expression Regulation Laboratory, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Corresponding authors: W. Timothy Garvey, , and Ching-Yi Chen, .
Brown adipose tissue oxidizes chemical energy for heat generation and energy expenditure. Promoting brown-like 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 1α, 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 post-transcriptional regulation of miR-150 expression.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1901/-/DC1.
- Received December 17, 2013.
- Accepted April 4, 2014.
- © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.