KSRP and MicroRNA 145 Are Negative Regulators of Lipolysis in White Adipose Tissue

Abstract

White adipose tissue (WAT) releases fatty acids from stored triacylglycerol for an energy source. Here, we report that targeted deletion of KH-type splicing regulatory protein (KSRP), an RNA-binding protein that regulates gene expression at multiple levels, enhances lipolysis in epididymal WAT (eWAT) because of the upregulation of genes promoting lipolytic activity. Expression of microRNA 145 (miR-145) is decreased because of impaired primary 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 posttranscriptional regulation of miR-145 expression.

ACKNOWLEDGMENTS

This work was supported by NIH grant GM068758 (C.-Y.C.) and grants from the Ministero della Salute (RF-2010-2306205) and AICR (10-0527) to R.G.