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PLIN5 deletion remodels intracellular lipid composition and causes insulin resistance in muscle

Abstract

Defective control of lipid metabolism leading to lipotoxicity causes insulin resistance in skeletal muscle, a major factor leading to diabetes. Here, we demonstrate that perilipin (PLIN) 5 is required to couple intramyocellular triacylglycerol lipolysis with the metabolic demand for fatty acids. PLIN5 ablation depleted triacylglycerol stores but increased sphingolipids including ceramide, hydroxylceramides and sphingomyelin. We generated perilipin 5 (Plin5)(-/-) mice to determine the functional significance of PLIN5 in metabolic control and insulin action. Loss of PLIN5 had no effect on body weight, feeding or adiposity but increased whole-body carbohydrate oxidation. Plin5 (-/-) mice developed skeletal muscle insulin resistance, which was associated with ceramide accumulation. Liver insulin sensitivity was improved in Plin5 (-/-) mice, indicating tissue-specific effects of PLIN5 on insulin action. We conclude that PLIN5 plays a critical role in coordinating skeletal muscle triacylglycerol metabolism, which impacts sphingolipid metabolism, and is requisite for the maintenance of skeletal muscle insulin action.

Type Journal
ISBN 2212-8778 (Electronic) 2212-8778 (Linking)
Authors Mason, R. R.; Mokhtar, R.; Matzaris, M.; Selathurai, A.; Kowalski, G. M.; Mokbel, N.; Meikle, P. J.; Bruce, C. R.; Watt, M. J.;
Publisher Name Molecular Metabolism
Published Date 2014-01-01 00:00:00
Published Volume 3
Published Issue 6
Published Pages 652-63
URL http://www.ncbi.nlm.nih.gov/pubmed/25161888
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?12597_13041/2014-Mason-Mol Metab.pdf