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

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


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.

Keywords: adiposity rebound; caloric restriction; exercise; glucocorticoid antagonism; glucose intolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / drug effects
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
  • Adiposity / drug effects*
  • Animals
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Blotting, Western
  • Body Weight / drug effects
  • Caloric Restriction*
  • Gluconeogenesis / drug effects
  • Glucose Intolerance / metabolism
  • Glucose Tolerance Test
  • Glycogen / metabolism
  • Glycogenolysis / drug effects
  • Hormone Antagonists / pharmacology*
  • Insulin / metabolism
  • Insulin Resistance
  • Intra-Abdominal Fat / drug effects*
  • Lipolysis / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mifepristone / pharmacology*
  • Physical Conditioning, Animal*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucocorticoid / antagonists & inhibitors


  • Blood Glucose
  • Hormone Antagonists
  • Insulin
  • Receptors, Glucocorticoid
  • Mifepristone
  • Glycogen
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1