title: Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training.
abstract: Cytoplasmic lipid droplets provide a reservoir for triglyceride storage and are a central hub for fatty acid trafficking in cells. The protein perilipin 5 (PLIN5) is highly expressed in oxidative tissues such as skeletal muscle and regulates lipid metabolism by coordinating the trafficking and the reversible interactions of effector proteins at the lipid droplet. PLIN5 may also regulate mitochondrial function, although this remains unsubstantiated. Hence, the aims of this study were to examine the role of PLIN5 in the regulation of skeletal muscle substrate metabolism during acute exercise and to determine whether PLIN5 is required for the metabolic adaptations and enhancement in exercise tolerance following endurance exercise training. Using muscle-specific Plin5 knockout mice (Plin5(MKO)), we show that PLIN5 is dispensable for normal substrate metabolism during exercise, as reflected by levels of blood metabolites and rates of glycogen and triglyceride depletion that were indistinguishable from control (lox/lox) mice. Plin5(MKO) mice exhibited a functional impairment in their response to endurance exercise training, as reflected by reduced maximal running capacity (20%) and reduced time to fatigue during prolonged submaximal exercise (15%). The reduction in exercise performance was not accompanied by alterations in carbohydrate and fatty acid metabolism during submaximal exercise. Similarly, mitochondrial capacity (mtDNA, respiratory complex proteins, citrate synthase activity) and mitochondrial function (oxygen consumption rate in muscle fiber bundles) were not different between lox/lox and Plin5(MKO) mice. Thus, PLIN5 is dispensable for normal substrate metabolism during exercise and is not required to promote mitochondrial biogenesis or enhance the cellular adaptations to endurance exercise training.
authors.affiliation: Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, and Department of Physiology, Monash University, Clayton, Victoria, Australia; Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, Sabah, Malaysia; and.
authors.forename: Ruzaidi A M
authors.initials: RA
authors.lastname: Mohktar
authors.affiliation: Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, and Department of Physiology, Monash University, Clayton, Victoria, Australia;
authors.forename: Magda K
authors.initials: MK
authors.lastname: Montgomery
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Murphy
authors.affiliation: Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, and Department of Physiology, Monash University, Clayton, Victoria, Australia; matthew.watt@monash.edu.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Watt
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D050260:Carbohydrate Metabolism / Q000235:genetics; D017079:Exercise Tolerance / Q000235:genetics*; D005227:Fatty Acids / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism*; D001678:Organelle Biogenesis; D010101:Oxygen Consumption / Q000235:genetics; D010805:Physical Conditioning, Animal; D012420:Running; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D014280:Triglycerides; C551268:lipid storage droplet protein 5, mouse; D006003:Glycogen
keywords: lipid metabolism; mitochondrial; perilipin 5; triglyceride