Brown adipose tissue oxidizes chemical energy for heat generation and energy expenditure. Promoting brownlike 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 1a, 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 posttranscriptional regulation of miR-150 expression.
KSRP ablation enhances brown fat gene program in white adipose tissue through reduced miR-150 expression / C. Chou, Y. Lin, H. Wang, X. Zhu, M. Giovarelli, P. Briata, R. Gherzi, W.T. Garvey, C. Chen. - In: DIABETES. - ISSN 0012-1797. - 63:9(2014 Sep), pp. 2949-2961.
|Titolo:||KSRP ablation enhances brown fat gene program in white adipose tissue through reduced miR-150 expression|
|Parole Chiave:||Adipose Tissue, Brown; Adipose Tissue, White; Adiposity; Animals; DNA-Binding Proteins; Diet, High-Fat; Down-Regulation; Gene Expression Regulation; Male; Mice; MicroRNAs; Obesity; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; RNA-Binding Proteins; Trans-Activators; Transcription Factors; Up-Regulation; Internal Medicine; Endocrinology, Diabetes and Metabolism|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Data di pubblicazione:||set-2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.2337/db13-1901|
|Appare nelle tipologie:||01 - Articolo su periodico|