Laboratorio de Investigación en Nutrición y Actividad Física (LABINAF), Instituto de Nutrición y Tecnologia de los Alimentos (INTA), Universidad de Chile, Santiago 7830490, Chile.
Departamento de Tecnología Medica, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile.
Int J Mol Sci. 2020 Oct 14;21(20):7582. doi: 10.3390/ijms21207582.
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.
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.
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.
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.
糖皮质激素（GCs）是能量平衡的关键调节剂。它们的失调与肥胖和代谢综合征的发展有关。然而，目前尚不清楚肥胖是否会改变组织糖皮质激素受体（GR）的反应，也不知道适度的有氧运动是否可以防止肥胖引起的 GR 反应改变。
为了评估肥胖小鼠的 GR 反应，我们用高脂肪饮食（HFD）喂养 C57BL6J 小鼠 12 周。在处死小鼠之前，我们给它们注射了地塞米松。为了评估运动在 GR 反应中的作用，我们用 HFD 喂养小鼠，并让它们每周进行三次适度的有氧运动。
我们发现，用高脂肪饮食喂养 12 周的小鼠出现了肝 GC 超敏反应，而胃筋肌或附睾脂肪 GR 反应没有变化。因此，适度的有氧运动改善了葡萄糖耐量，增加了皮质酮的血浆水平，并通过增加附睾脂肪 GR 反应来预防肝 GR 超敏反应。
总的来说，我们的结果表明，高脂肪饮食诱导肥胖的小鼠出现了肝 GR 敏感性，这可能会增强高脂肪饮食在肝脏中的代谢作用。此外，运动被发现是一种可行的非药物策略，可以防止肥胖引起的 GR 反应失调。
