Voluntary wheel running in the late dark phase ameliorates diet-induced obesity in mice without altering insulin action

Metabolic dysfunction and Type 2 diabetes are associated with perturbed circadian rhythms. However, exercise appears to ameliorate circadian disturbances, as it can phase-shift or reset the internal clock system. Evidence is emerging that exercise at a distinct time of day can correct misalignments of the circadian clock and influence energy metabolism. This suggests that timing of exercise training can be important for the prevention and management of metabolic dysfunction. In this study, obese, high-fat diet-fed mice were subjected to voluntary wheel running (VWR) at two different periods of the day to determine the effects of time-of-day-restricted VWR on basal and insulin-stimulated glucose disposal. VWR in the late dark phase reduced body weight gain compared with VWR in the beginning of the dark phase. Conversely, time-of-day-restricted VWR did not influence insulin action and glucose disposal, since skeletal muscle and adipose tissue glucose uptake and insulin signaling remained unaffected. Protein abundance of the core clock proteins, brain-muscle arnt-like 1 (BMAL1), and circadian locomotor output control kaput (CLOCK), were increased in skeletal muscle after VWR, independent of whether mice had access to running wheels in the early or late dark phase. Collectively, we provide evidence that VWR in the late dark phase ameliorates diet-induced obesity without altering insulin action or glucose homeostasis. NEW & NOTEWORTHY Exercise appears to ameliorate circadian disturbances as it can entrain the internal clock system. We provide evidence that voluntary wheel running increases core clock protein abundance and influences diet-induced obesity in mice in a time-of-day-dependent manner. However, the effect of time-of-day-restricted voluntary wheel running on body weight gain is not associated with enhanced basal- and insulin-stimulated glucose disposal, suggesting that time-of-day-restricted voluntary wheel running affects energy homeostasis rather than glucose homeostasis.