Exercise Training Impacts Skeletal Muscle Clock Machinery in Prediabetes.

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.