(CSEMP011) METABOLIC CONSEQUENCES OF EXERCISE CESSATION

Background: Transitioning from regular physical activity to inactivity increases risk factors for type 2 diabetes such as insulin resistance, hyperinsulinemia, and obesity, however, the underlying mechanisms remain poorly understood. Hyperinsulinemia is often considered to occur in response to insulin resistance; however, recent studies suggest that hyperinsulinemia plays a causal role in the development of insulin resistance and obesity. Hyperinsulinemia following a transition to inactivity may therefore drive risk factors for diabetes.

METHODS AND RESULTS: Both female and male C57BL/6J mice were fed a high fat/high sucrose diet from 12 weeks of age and housed under thermoneutral conditions (28°C). Mice had access to a running wheel for 4 weeks, prior to the wheel being locked for 7 days. Active and sedentary control groups were also included. Body composition was assessed at the beginning, wheel lock timepoint and end of the study while glucose homeostasis and insulin secretion were assessed at the end of the study. Upon sacrifice, adipose pads and liver were weighed and the pancreas was fixed for determining beta-cell proliferation and area using immunofluorescent staining. A rapid expansion of adiposity occurred following 7 days of wheel lock, with male and female mice having a 48±8% (mean±SEM) and 50±7% increase in fat mass, which approached levels seen in sedentary mice. An elevation in fasting insulin and insulin resistance (calculated using the homeostatic model assessment for insulin resistance) to near sedentary levels was also observed. A transition to inactivity in male mice led to significantly higher fasting glucose levels in comparison to both sedentary and active control groups, while glucose tolerance in female mice was comparable to that seen in sedentary mice following 7 days of wheel lock. Beta-cell mass was highest in mice following 7 days of wheel lock while beta-cell proliferation was found to be lower in active mice but increase to sedentary levels following a transition to inactivity.

Conclusion: These findings highlight that exercise cessation can rapidly increase risk factors for the development of type 2 diabetes such as hyperinsulinemia, impaired glucose tolerance and increased adiposity. Current studies are now being performed with this model of exercise cessation to study the causal role of hyperinsulinemia in the development of metabolic dysfunction and the underlying mechanisms by which exercise and exercise cessation modify beta-cell function and alter the risk of diabetes.