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

Alejandra Espinosa,Rodrigo Troncoso,Francisco Díaz-Castro,Pamela Pino,Francisco Pino-De La Fuente,Camila Donoso-Barraza,Jonatan Dassonvalle,Carlos Sepúlveda,Mario Chiong,Miguel Llanos

doi:10.3390/ijms21207582

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.

Highlights

Obesity is excess or abnormal fat accumulation that increases the risk of developing insulin resistance, type 2 diabetes, cancer, and cardiovascular disease, among others [1]
Corticosterone Plasmatic Levels Were Altered in High-Fat Diet Mice The effect of high-fat diet (HFD)-induced obesity in GCs response was evaluated in C57BL/6J male mice fed for
We investigated the effect of HFD-induced obesity in the GC response in the liver, skeletal muscle, and adipose tissue

Summary

Introduction

Obesity is excess or abnormal fat accumulation that increases the risk of developing insulin resistance, type 2 diabetes, cancer, and cardiovascular disease, among others [1]. Several endogenous and exogenous factors can favor a positive energy balance and weight gains, such as metabolic inflexibility, stress, endocrine deregulations, poor sleep, and medicines with weight gain as a side effect [2,3,4,5,6]. It implies deregulation of several biological systems involved in the energy homeostasis [7]. GCs are critical regulators of energy balance; part of their actions on metabolism are through catabolic activity. The Krüppel-like factor 15 (KLF15) is a transcription factor that controls the main pathways of amino acid, glucose, and lipid metabolism, and mediates the ergogenic effects of GCs [16]

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Conclusion