Moderate Aerobic Exercise Training Prevents the Augmented Hepatic Glucocorticoid Response Induced by High-Fat Diet in Mice

Abstract

Glucocorticoids (GCs) are critical regulators of energy balance. Their deregulation is associated with the development of obesity and metabolic syndrome. However, it is not understood if obesity alters the tissue glucocorticoid receptor (GR) response, and moreover whether a moderate aerobic exercise prevents the alteration in GR response induced by obesity. Methods: To evaluate the GR response in obese mice, we fed C57BL6J mice with a high-fat diet (HFD) for 12 weeks. Before mice were sacrificed, we injected them with dexamethasone. To assess the exercise role in GR response, we fed mice an HFD and subjected them to moderate aerobic exercise three times a week. Results: We found that mice fed a high-fat diet for 12 weeks developed hepatic GC hypersensitivity without changes in the gastrocnemius or epididymal fat GR response. Therefore, moderate aerobic exercise improved glucose tolerance, increased the corticosterone plasma levels, and prevented hepatic GR hypersensitivity with an increase in epididymal fat GR response. Conclusion: Collectively, our results suggest that mice with HFD-induced obesity develop hepatic GR sensitivity, which could enhance the metabolic effects of HFD in the liver. Moreover, exercise was found to be a feasible non-pharmacological strategy to prevent the deregulation of GR response in obesity.

Hepatic Gadd45β promotes hyperglycemia and glucose intolerance through DNA demethylation of PGC-1α

“…Plasma corticosterone levels are usually higher in db/db and ob/ob mice, compared with normal lean mice ( Liu et al, 2003 ; Liu et al, 2005 ; Liu et al, 2006 ). Besides, while no significant differences in circulating corticosterone concentration between mice fed an HFD and normal chow diet, hepatic GR signaling or sensitivity was enhanced in the livers of HFD-induced obese mice ( Quagliarini et al, 2019 ; Dassonvalle et al, 2020 ). As expected, these mice displayed hyperglycemia and insulin resistance, which were described in our previous study ( Lu et al, 2014 ).…”

Is Physical Activity an Efficient Strategy to Control the Adverse Effects of Persistent Organic Pollutants in the Context of Obesity? A Narrative Review

“…Interestingly, some POPs may disrupt GR expression [40]. Independently of the effect of POPs, the protective effect of PA on GR has already been established [41]. Although studies seem to indicate that GR and POPs can interact with each other [42], the ability of PA to counteract the adverse effects of POPs via an effect on GR remains to be established.…”

Is Physical Activity an Efficient Strategy to Control the Adverse Effects of Persistent Organic Pollutants in the Context of Obesity? A Narrative Review

“…In an interesting manner, some POPs may disrupt GR expression [37]. Independently of the effect of POPs, the protective effect of PA on GR has already been established [38]. Although studies seem to indicate that GR and POPs can interact with each other [39], the ability of PA to counteract the adverse effects of POPs via an effect on GR remains to be established.…”