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Mol Metab. 2014 Jun 14;3(6):652-63. doi: 10.1016/j.molmet.2014.06.002. eCollection 2014 Sep.

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

Author information

1
Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, 3800, Australia.
2
Garvan Institute of Medical Research, Darlinghurst., New South Wales, 2006, Australia.
3
Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, 3004, Australia.

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.

KEYWORDS:

Insulin resistance; Lipid droplet; Lipid metabolism; Perilipin; Skeletal muscle

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