Mohktar Ruzaidi A M, Montgomery Magda K, Murphy Robyn M, Watt Matthew J
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.
Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, and Department of Physiology, Monash University, Clayton, Victoria, Australia;
Am J Physiol Endocrinol Metab. 2016 Jul 1;311(1):E128-37. doi: 10.1152/ajpendo.00084.2016. Epub 2016 May 17.
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.
细胞质脂滴为甘油三酯储存提供了一个库，并且是细胞内脂肪酸运输的核心枢纽。蛋白围脂滴蛋白5（PLIN5）在诸如骨骼肌等氧化组织中高度表达，并通过协调效应蛋白在脂滴处的运输及可逆相互作用来调节脂质代谢。PLIN5也可能调节线粒体功能，尽管这一点尚未得到证实。因此，本研究的目的是探究PLIN5在急性运动期间对骨骼肌底物代谢调节中的作用，并确定耐力运动训练后代谢适应及运动耐力增强是否需要PLIN5。使用肌肉特异性Plin5基因敲除小鼠（Plin5（MKO）），我们发现，运动期间PLIN5对于正常底物代谢并非必需，这一点由血液代谢物水平以及糖原和甘油三酯消耗速率所反映，这些指标与对照（lox/lox）小鼠并无差异。Plin5（MKO）小鼠在对耐力运动训练的反应中表现出功能受损，这一点由最大跑步能力降低（20%）以及在长时间次最大运动期间疲劳时间缩短（15%）所反映。运动表现的降低并未伴随着次最大运动期间碳水化合物和脂肪酸代谢的改变。同样，lox/lox小鼠和Plin5（MKO）小鼠之间的线粒体容量（线粒体DNA、呼吸复合体蛋白、柠檬酸合酶活性）和线粒体功能（肌纤维束中的氧气消耗率）并无差异。因此，运动期间PLIN5对于正常底物代谢并非必需，并且促进线粒体生物发生或增强细胞对耐力运动训练的适应并不需要PLIN5。
