title: 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.
authors.affiliation: Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, 3800, Australia.
authors.forename: Rachael R
authors.initials: RR
authors.lastname: Mason
authors.affiliation: Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, 3800, Australia.
authors.forename: Ruzaidi
authors.initials: R
authors.lastname: Mokhtar
authors.affiliation: Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, 3800, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Matzaris
authors.affiliation: Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, 3800, Australia.
authors.forename: Ahrathy
authors.initials: A
authors.lastname: Selathurai
authors.affiliation: Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, 3800, Australia.
authors.forename: Greg M
authors.initials: GM
authors.lastname: Kowalski
authors.affiliation: Garvan Institute of Medical Research, Darlinghurst., New South Wales, 2006, Australia.
authors.forename: Nancy
authors.initials: N
authors.lastname: Mokbel
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, 3004, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
authors.affiliation: Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, 3800, Australia.
authors.forename: Clinton R
authors.initials: CR
authors.lastname: Bruce
authors.affiliation: Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, 3800, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Watt
keywords: Insulin resistance; Lipid droplet; Lipid metabolism; Perilipin; Skeletal muscle