Exercise Intervention Reduces Circadian Clock Suppressor, CRY2, in Adults with Obesity

Abstract

PURPOSE: Exercise improves skeletal muscle insulin sensitivity, and also resets physiological circadian clocks. CRY2, a circadian clock suppressor, reduces exercise capacity in mouse models. Whether exercise impacts CRY2 in humans is unknown. Thus, we tested the effects of 12 weeks of exercise training on circulating CRY2 concentrations in adults with obesity. Secondarily, we assessed whether these changes were related to improvements in insulin sensitivity. METHODS: Thirteen adults (Age: 64.4 ± 13.7, BMI: 35.9 ± 5.1) participated in 12 weeks of exercise training (5 day/wk, 60 min/session, 85% HRmax) combined with a eucaloric diet. Body composition (abdominal adiposity using computed tomography), insulin sensitivity (glucose disposal rate from euglycemic-hyperinsulinemic clamp), exercise capacity (VO2max), and circulating CRY2 levels measured by ELISA were assessed before and after intervention. RESULTS: Body composition (BMI, abdominal adiposity), insulin sensitivity, and exercise capacity all improved (all P > 0.05). CRY2 levels decreased after intervention (Pre: 12.2 ± 2.1; Post: 10.1 ± 2.3 ng/mL; P=0.001). Baseline CRY2 inversely correlated with baseline fat-free mass (r=-0.56, P=0.046) and baseline insulin sensitivity (r=-0.61, P=0.038). CONCLUSION: We show for the first time that exercise training reduces circulating levels of CRY2, a circadian clock suppressor, in adults with obesity, which was accompanied by increased insulin sensitivity and improved body composition. Direct links between exercise-induced changes in circadian clock function and parallel systemic metabolic improvements are worthy of further investigation. Funding: Supported by NIH grant R01 AG12834, and in part by CTSA 1UL1RR024989 and U54 GM104940.