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

Chu Fang Chou, Yi Yu Lin, Hsu Kun Wang, Xiaolin Zhu, Matteo Giovarelli, Paola Briata, Roberto Gherzi, W. Timothy Garvey, Ching Yi Chen

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2949-2961
Number of pages13
JournalDiabetes
Volume63
Issue number9
DOIs
Publication statusPublished - 2014

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Protein Splicing
White Adipose Tissue
Brown Adipose Tissue
MicroRNAs
Groin
Genes
RNA-Binding Proteins
PPAR gamma
Adiposity
Energy Metabolism
Obesity
Hot Temperature
Gene Expression

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Chou, C. F., Lin, Y. Y., Wang, H. K., Zhu, X., Giovarelli, M., Briata, P., ... Chen, C. Y. (2014). KSRP ablation enhances brown fat gene program in white adipose tissue through reduced miR-150 expression. Diabetes, 63(9), 2949-2961. https://doi.org/10.2337/db13-1901

KSRP ablation enhances brown fat gene program in white adipose tissue through reduced miR-150 expression. / Chou, Chu Fang; Lin, Yi Yu; Wang, Hsu Kun; Zhu, Xiaolin; Giovarelli, Matteo; Briata, Paola; Gherzi, Roberto; Garvey, W. Timothy; Chen, Ching Yi.

In: Diabetes, Vol. 63, No. 9, 2014, p. 2949-2961.

Research output: Contribution to journalArticle

Chou, CF, Lin, YY, Wang, HK, Zhu, X, Giovarelli, M, Briata, P, Gherzi, R, Garvey, WT & Chen, CY 2014, 'KSRP ablation enhances brown fat gene program in white adipose tissue through reduced miR-150 expression', Diabetes, vol. 63, no. 9, pp. 2949-2961. https://doi.org/10.2337/db13-1901
Chou, Chu Fang ; Lin, Yi Yu ; Wang, Hsu Kun ; Zhu, Xiaolin ; Giovarelli, Matteo ; Briata, Paola ; Gherzi, Roberto ; Garvey, W. Timothy ; Chen, Ching Yi. / KSRP ablation enhances brown fat gene program in white adipose tissue through reduced miR-150 expression. In: Diabetes. 2014 ; Vol. 63, No. 9. pp. 2949-2961.
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