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


ABSTRACT: 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 1?, 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.

SUBMITTER: Chou CF 

PROVIDER: S-EPMC4141372 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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

Chou Chu-Fang CF   Lin Yi-Yu YY   Wang Hsu-Kun HK   Zhu Xiaolin X   Giovarelli Matteo M   Briata Paola P   Gherzi Roberto R   Garvey W Timothy WT   Chen Ching-Yi CY  

Diabetes 20140410 9


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(  ...[more]

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