title: Glucocorticoid antagonism limits adiposity rebound and glucose intolerance in young male rats following the cessation of daily exercise and caloric restriction.
abstract: 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.
authors.affiliation: Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada;
authors.forename: Trevor
authors.initials: T
authors.lastname: Teich
authors.affiliation: Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada;
authors.forename: Emily C
authors.initials: EC
authors.lastname: Dunford
authors.affiliation: Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada;
authors.forename: Deanna P
authors.initials: DP
authors.lastname: Porras
authors.affiliation: Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada;
authors.forename: Jacklyn A
authors.initials: JA
authors.lastname: Pivovarov
authors.affiliation: Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; and.
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Beaudry
authors.affiliation: Corcept Therapeutics, Menlo Park, California.
authors.forename: Hazel
authors.initials: H
authors.lastname: Hunt
authors.affiliation: Corcept Therapeutics, Menlo Park, California.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Belanoff
authors.affiliation: Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada; mriddell@yorku.ca.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Riddell
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D031204:Caloric Restriction; D005943:Gluconeogenesis / Q000187:drug effects; D018149:Glucose Intolerance / Q000378:metabolism; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D050261:Glycogenolysis / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects*; D008066:Lipolysis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors
chemical_list: D001786:Blood Glucose; D006727:Hormone Antagonists; D007328:Insulin; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D006003:Glycogen; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1
keywords: adiposity rebound; caloric restriction; exercise; glucocorticoid antagonism; glucose intolerance