Integrative Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA.
Med Sci Sports Exerc. 2020 Oct;52(10):2078-2085. doi: 10.1249/MSS.0000000000002368.
Disruption of the skeletal muscle molecular clock leads to metabolic disease, whereas exercise may be restorative, leading to improvements in metabolic health. The purpose of this study was to evaluate the effects of a 12-wk exercise intervention on skeletal muscle molecular clock machinery in adults with obesity and prediabetes, and determine whether these changes were related to exercise-induced improvements in metabolic health.
Twenty-six adults (age, 66 ± 4.5 yr; body mass index (BMI), 34 ± 3.4 kg·m; fasting plasma glucose, 105 ± 15 mg·dL) participated in a 12-wk exercise intervention and were fully provided isoenergetic diets. Body composition (dual x-ray absorptiometry), abdominal adiposity (computed tomography scans), peripheral insulin sensitivity (euglycemic-hyperinsulinemic clamp), exercise capacity (maximal oxygen consumption), and skeletal muscle molecular clock machinery (vastus lateralis biopsy) were assessed at baseline and after intervention. Gene and protein expression of skeletal muscle BMAL1, CLOCK, CRY1/2, and PER 1/2 were measured by quantitative real-time polymerase chain reaction and Western blot, respectively.
Body composition (BMI, dual x-ray absorptiometry, computed tomography), peripheral insulin sensitivity (glucose disposal rate), and exercise capacity (maximal oxygen consumption) all improved (P < 0.005) with exercise training. Skeletal muscle BMAL1 gene (fold change, 1.62 ± 1.01; P = 0.027) and PER2 protein expression (fold change, 1.35 ± 0.05; P = 0.02) increased, whereas CLOCK, CRY1/2, and PER1 were unchanged. The fold change in BMAL1 correlated with post-glucose disposal rate (r = 0.43, P = 0.044), BMI (r = -0.44, P = 0.042), and body weight changes (r = -0.44, P = 0.039) expressed as percent delta.
Exercise training impacts skeletal muscle molecular clock machinery in a clinically relevant cohort of adults with obesity and prediabetes. Skeletal muscle BMAL1 gene expression may improve insulin sensitivity. Future studies are needed to determine the physiological significance of exercise-induced alterations in skeletal muscle clock machinery.
骨骼肌分子钟的破坏会导致代谢疾病，而运动则可能具有修复作用，从而改善代谢健康。本研究的目的是评估 12 周运动干预对肥胖和糖尿病前期成年人骨骼肌分子钟机制的影响，并确定这些变化是否与运动引起的代谢健康改善有关。
26 名成年人（年龄 66 ± 4.5 岁；体重指数（BMI）34 ± 3.4 kg·m；空腹血糖 105 ± 15 mg·dL）参加了 12 周的运动干预，并接受了完全提供等热量饮食。在基线和干预后评估身体成分（双能 X 线吸收法）、腹部脂肪（计算机断层扫描）、外周胰岛素敏感性（正葡萄糖高胰岛素钳夹）、运动能力（最大耗氧量）和骨骼肌分子钟机制（股外侧肌活检）。通过定量实时聚合酶链反应和 Western blot 分别测量骨骼肌 BMAL1、CLOCK、CRY1/2 和 PER 1/2 的基因和蛋白表达。
身体成分（BMI、双能 X 线吸收法、计算机断层扫描）、外周胰岛素敏感性（葡萄糖处置率）和运动能力（最大耗氧量）均随运动训练而改善（P < 0.005）。骨骼肌 BMAL1 基因（倍数变化，1.62 ± 1.01；P = 0.027）和 PER2 蛋白表达（倍数变化，1.35 ± 0.05；P = 0.02）增加，而 CLOCK、CRY1/2 和 PER1 不变。BMAL1 的倍数变化与葡萄糖处置率后（r = 0.43，P = 0.044）、BMI（r = -0.44，P = 0.042）和体重变化（r = -0.44，P = 0.039）呈正相关，以百分比变化表示。
运动训练对肥胖和糖尿病前期成年人骨骼肌分子钟机制产生了临床相关的影响。骨骼肌 BMAL1 基因表达可能改善胰岛素敏感性。需要进一步的研究来确定运动引起的骨骼肌时钟机制改变的生理意义。
