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 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.
journal_name
Diabetesjournal_title
Diabetesauthors
Chou CF,Lin YY,Wang HK,Zhu X,Giovarelli M,Briata P,Gherzi R,Garvey WT,Chen CYdoi
10.2337/db13-1901subject
Has Abstractpub_date
2014-09-01 00:00:00pages
2949-61issue
9eissn
0012-1797issn
1939-327Xpii
db13-1901journal_volume
63pub_type
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