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Am J Physiol Endocrinol Metab. 2016 Jul 1;311(1):E56-68. doi: 10.1152/ajpendo.00490.2015. Epub 2016 May 3.

Glucocorticoid antagonism limits adiposity rebound and glucose intolerance in young male rats following the cessation of daily exercise and caloric restriction.

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Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada;
Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; and.
Corcept Therapeutics, Menlo Park, California.
Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada;


Severe caloric restriction (CR), in a setting of regular physical exercise, may be a stress that sets the stage for adiposity rebound and insulin resistance when the food restriction and exercise stop. In this study, we examined the effect of mifepristone, a glucocorticoid (GC) receptor antagonist, on limiting adipose tissue mass gain and preserving whole body insulin sensitivity following the cessation of daily running and CR. We calorically restricted male Sprague-Dawley rats and provided access to voluntary running wheels for 3 wk followed by locking of the wheels and reintroduction to ad libitum feeding with or without mifepristone (80 mg·kg(-1)·day(-1)) for 1 wk. Cessation of daily running and CR increased HOMA-IR and visceral adipose mass as well as glucose and insulin area under the curve during an oral glucose tolerance test vs. pre-wheel lock exercised rats and sedentary rats (all P < 0.05). Insulin sensitivity and glucose tolerance were preserved and adipose tissue mass gain was attenuated by daily mifepristone treatment during the post-wheel lock period. These findings suggest that following regular exercise and CR there are GC-induced mechanisms that promote adipose tissue mass gain and impaired metabolic control in healthy organisms and that this phenomenon can be inhibited by the GC receptor antagonist mifepristone.


adiposity rebound; caloric restriction; exercise; glucocorticoid antagonism; glucose intolerance

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