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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.

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


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.


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

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