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.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Adipocytes / cytology
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Adipocytes / metabolism
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Adipose Tissue, White / metabolism*
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Adiposity
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Animals
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Cell Differentiation
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Cell Size
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Down-Regulation / genetics
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Epididymis / metabolism
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Fatty Acids / metabolism
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Forkhead Box Protein O1
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Forkhead Transcription Factors / metabolism
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Gene Deletion
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Lipolysis / genetics*
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Male
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Mice
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Mice, Inbred C57BL
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Organ Size
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Oxidation-Reduction
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RNA Processing, Post-Transcriptional / genetics
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RNA-Binding Proteins / metabolism*
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Thermogenesis / genetics
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Trans-Activators / deficiency
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Trans-Activators / metabolism*
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Triglycerides / metabolism
Substances
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Fatty Acids
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Foxo1 protein, mouse
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Khsrp protein, mouse
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MIRN145a microRNA, mouse
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MicroRNAs
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RNA-Binding Proteins
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Trans-Activators
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Triglycerides