All ETDs from UAB

Advisory Committee Chair

Ching-Yi Chen

Advisory Committee Members

David M Bedwell

Louise T Chow

Hengbin Wang

Martin E Young

Document Type

Dissertation

Date of Award

2014

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

White adipose tissue (WAT) releases fatty acids from stored triacylglycerol (TAG) for energy source. Here, we report that null mice for KH-type splicing regulatory protein (KSRP), an RNA-binding protein, resisted high fat diet (HFD) induced obesity. Target of deletion of KSRP regulates gene expression at multiple levels and enhances lipolysis in epididymal WAT (eWAT) due to up-regulation of genes promoting lipolytic activity. Expression of miR-145 is decreased due to impaired pri-miR-145 processing in Ksrp-/- eWAT. We show that miR-145 directly targets and represses Foxo1 and Cgi58, activators of lipolytic activity, and forced expression of miR-145 attenuates lipolysis. This study reveals a novel in vivo function of KSRP in controlling adipose lipolysis through post-transcriptional regulation of miR-145 expression.

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