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 & Molecular Genetics
- 2Department of Nutrition Sciences University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
- 3Gene Expression Regulation Laboratory, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy
- *Corresponding Author: W. Timothy Garvey, E-mail: and Ching-Yi Chen, E-mail:
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.
- © 2014 by the American Diabetes Association.
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