PLIN5 deletion remodels intracellular lipid composition and causes insulin resistance in muscle
AuthorMason, RR; Mokhtar, R; Matzaris, M; Selathurai, A; Kowalski, GM; Mokbel, N; Meikle, PJ; Bruce, CR; Watt, MJ
Source TitleMolecular Metabolism
Document TypeJournal Article
CitationsMason, R. R., Mokhtar, R., Matzaris, M., Selathurai, A., Kowalski, G. M., Mokbel, N., Meikle, P. J., Bruce, C. R. & Watt, M. J. (2014). PLIN5 deletion remodels intracellular lipid composition and causes insulin resistance in muscle. MOLECULAR METABOLISM, 3 (6), pp.652-663. https://doi.org/10.1016/j.molmet.2014.06.002.
Access StatusOpen Access
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.
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