Dirks Marlou L, Stephens Francis B, Jackman Sarah R, Galera Gordo Jesús, Machin David J, Pulsford Richard M, van Loon Luc J C, Wall Benjamin T
Department of Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK.
Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
Exp Physiol. 2018 Jun;103(6):860-875. doi: 10.1113/EP086961.
What is the central question of this study? What are the initial metabolic and molecular events that underpin bed rest-induced skeletal muscle deconditioning, and what is the contribution of energy balance? What is the main finding and its importance? A single day of bed rest, irrespective of energy balance, did not lead to overt changes in skeletal muscle gene expression or insulin sensitivity. More than 1 day of physical inactivity is required to observe the insulin resistance and robust skeletal muscle transcriptional responses associated with bed rest and consequent alterations in energy balance.
The initial metabolic and molecular events that underpin disuse-induced skeletal muscle deconditioning, and the contribution of energy balance, remain to be investigated. Ten young, healthy men (age 25 ± 1 years; body mass index 25.3 ± 0.8 kg·m ) underwent three 24 h laboratory-based experimental periods in a randomized, crossover manner: (i) controlled habitual physical activity with an energy-balanced diet (CON); (ii) strict bed rest with a diet to maintain energy balance (BR-B); and (iii) strict bed rest with a diet identical to CON, consequently resulting in positive energy balance. Continuous glucose monitoring was performed throughout each visit, with vastus lateralis muscle biopsies and an oral glucose tolerance test performed before and after. In parallel with muscle samples collected from a previous 7 day bed rest study, biopsies were used to examine the expression of genes associated with the regulation of muscle mass and insulin sensitivity. A single day of bed rest, irrespective of energy balance, did not lead to overt changes in whole-body substrate oxidation, indices of insulin sensitivity [i.e. homeostatic model assessment of insulin resistance, BR-B from 2.7 ± 1.7 to 3.1 ± 1.5 (P > 0.05) and Matsuda index, BR-B from 5.9 ± 3.3 to 5.2 ± 2.9 (P > 0.05)] or 24 h glycaemic control/variability compared with CON. Seven days of bed rest led to ∼30-55% lower expression of genes involved in insulin signalling, lipid storage/oxidation and muscle protein breakdown, whereas no such changes were observed after 1 day of bed rest. In conclusion, more than a single day of physical inactivity is required to observe the insulin resistance and robust skeletal muscle transcriptional responses associated with bed rest and consequent alterations in energy balance.
本研究的核心问题是什么?导致卧床休息引起骨骼肌失健的初始代谢和分子事件是什么,能量平衡在此过程中起到了什么作用?主要发现及其重要性是什么?无论能量平衡状况如何,单日卧床休息均未导致骨骼肌基因表达或胰岛素敏感性出现明显变化。需要超过1天的身体不活动状态,才能观察到与卧床休息及随之而来的能量平衡改变相关的胰岛素抵抗和骨骼肌强烈的转录反应。
导致废用性骨骼肌失健的初始代谢和分子事件以及能量平衡的作用仍有待研究。10名年轻健康男性(年龄25±1岁;体重指数25.3±0.8kg·m²)以随机交叉方式进行了3个基于实验室的24小时实验期:(i)能量平衡饮食下的对照习惯性身体活动(CON);(ii)能量平衡饮食下的严格卧床休息(BR-B);(iii)与CON相同饮食下的严格卧床休息,从而导致正能量平衡。每次访视期间均进行连续血糖监测,并在前后进行股外侧肌活检和口服葡萄糖耐量试验。与之前一项7天卧床休息研究收集的肌肉样本并行,活检样本用于检测与肌肉量调节和胰岛素敏感性相关基因的表达。无论能量平衡状况如何,单日卧床休息均未导致全身底物氧化、胰岛素敏感性指标[即胰岛素抵抗稳态模型评估,BR-B组从2.7±1.7变为3.1±1.5(P>0.05);松田指数,BR-B组从5.9±3.3变为5.2±2.9(P>0.05)]或24小时血糖控制/变异性与CON组相比出现明显变化。7天卧床休息导致参与胰岛素信号传导、脂质储存/氧化和肌肉蛋白分解的基因表达降低约30-55%,而单日卧床休息后未观察到此类变化。总之,需要超过单日的身体不活动状态,才能观察到与卧床休息及随之而来的能量平衡改变相关的胰岛素抵抗和骨骼肌强烈的转录反应。