Paper of the Month - March 2017

Teich T, Dunford EC, Porras DP, Pivovarov JA, Beaudry JL, Hunt H, Belanoff JK, Riddell MC. 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.

From the authors: "Weight regain following successful weight loss is a common and significant challenge. Although caloric restriction (CR) (i.e. ‘dieting’) and regular exercise can induce weight loss, lower body fat, as well as improve overall health, a key component to their success is adherence. Human and rodent studies have observed a rapid induction of insulin resistance, glucose intolerance, and visceral fat growth once regular exercise and CR is stopped. Thus, rapid cessation of a lifestyle intervention may precipitate a rapid regrowth of adipose tissue as well as cause impaired metabolic health. Sustained elevations in glucocorticoids (GC’s) (i.e. ‘stress hormones’) are well known to induce insulin resistance as well as a selective growth of visceral fat mass. Previous studies from our lab and others have observed that increased physical activity is associated with elevated activity and content of the enzyme 11β-HSD1 both systemically and within visceral adipose tissue. This enzyme selectively converts stress hormones from their inactive to active state locally within a tissue. We hypothesized that elevations in GC’s following regular exercise and dieting contribute to the weight regain and body fat regrowth phenomenon.

In this study, we examined the effects of mifepristone, a GC receptor antagonist, on weight regain and metabolic health following cessation of regular exercise and CR in healthy male rats. We calorically restricted 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 daily) for 1 wk. Cessation of daily running and CR significantly increased  insulin resistance (as measured by HOMA-IR), visceral adipose tissue mass, as well as glucose and insulin area under the curve during an oral glucose tolerance test vs. rats that did not undergo detraining and vs. age-matched rats that served as sedentary controls (all P< 0.05). Insulin sensitivity and glucose tolerance were preserved and adipose tissue growth was significantly attenuated by mifepristone treatment during the wheel lock period.  These findings suggest that following the cessation of training and dieting there are stress-induced mechanisms that promote adipose tissue growth and impaired metabolic control in healthy organisms and that this phenomenon can be prevented by the GC receptor antagonist mifepristone."

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