PURPOSE:

Disruption of the skeletal muscle molecular clock leads to metabolic disease, while exercise may be restorative, leading to improvements in metabolic health. The purpose of this study was to evaluate the effects of a 12-week 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 yrs; BMI: 34±3.4 kg/m 2, FPG: 105±15 mg/dL) participated in a 12-week exercise intervention and were fully provided isoenergetic diets. Body composition (DXA), abdominal adiposity (CT scans), peripheral insulin sensitivity (euglycemic-hyperinsulinemic clamp), exercise capacity (VO 2 max), 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 PCR and Western blot, respectively.

RESULTS:

Body composition (BMI, DXA, CT), peripheral insulin sensitivity (glucose disposal rate; GDR), and exercise capacity (VO 2 max) 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, while CLOCK, CRY1/2 and PER1 were unchanged. The fold change in BMAL1 correlated with post GDR (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.

CONCLUSION:

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.