The Cessation of Daily Exercise and Caloric Restriction Causes Rapid Adiposity Rebound and Glucose Intolerance, Findings that are Abolished by Mifepristone

We tested the efficacy of mifepristone, a glucocorticoid (GC) receptor antagonist, on limiting adiposity rebound and preserving whole-body insulin sensitivity following the cessation of daily exercise and caloric restriction (CR). We calorically restricted male Sprague-Dawley rats and provided 24hr access to voluntary running wheels for three weeks followed by locking of the wheels and reintroduction to ad libitum feeding either with or without mifepristone (80 mg/kg/day) for one week. Cessation of daily running and CR increased HOMA-IR, visceral adipose mass as well as glucose and insulin area under the curve during an oral glucose tolerance test versus exercising rats (p<0.05). These findings were prevented or attenuated by daily mifepristone treatment during the post-wheel lock period. These findings suggest that elevations in GC action following regular exercise and CR promote rapid deterioration in metabolic control in healthy organisms and that this phenomenon can be inhibited by the GC receptor antagonist mifepristone.