Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common forms of liver disease, which is associated with several etiological factors, including stress and dysfunction in oxidative metabolism. However, studies showed that aerobic exercise training (AET) can combat the oxidative stress (OS) and improves mitochondrial functionality in the NAFLD. To test the hypothesis that AET improves oxidative metabolism and antioxidant defense in the liver of ob/ob mice. Male ob/ob mice with eight weeks old were separated into two groups: the sedentary group (S), n=7, and the trained group (T), n=7. The T mice were submitted to an 8-week protocol of AET at 60% of the maximum velocity achieved in the running capacity test. Before AET, no difference was observed in running test between the groups (S=10.4 ± 0.7 min vs. T= 13 ± 0.47 min). However, after AET, the running capacity was increased in the T group (12.8 ± 0.87 min) compared to the S group (7.2 ± 0.63 min). In skeletal muscle, the T group (26.91 ± 1.12 U/mg of protein) showed higher citrate synthase activity compared with the S group (19.28 ± 0.88 U/mg of protein) (p =0.006). In the analysis of BW evolution, significant reductions were seen in the T group as of the fourth week when compared to the S group. In addition, food intake was not significant different between the groups. Significant increases were observed in the activity of enzymes citrate synthase (p=0.004) and β-HAD (p=0.01) as well as in PGC-1α gene expression (p=0.002) in the liver of T group. The levels of TBARs and carbonyls, as well as SOD, CAT and GST were not different between the groups. However, in the nonenzymatic antioxidant system, we found that the T group had higher sulfhydryl (p = 0.02), GSH (p=0.001) and GSH/GSSG (p=0.02) activity. In conclusion, the AET improved body weight evolution and the aerobic capacity, increased the response of oxidative metabolism markers in the liver such as PGC-1α gene expression and citrate synthase and β-HAD enzyme activities in ob/ob mice. In addition, AET improved the non-enzymatic antioxidant defense and did not change the enzymatic defense.

Highlights

  • Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of intrahepatic lipids, reaching an absolute level of 5% of the total hepatic content [1, 2]

  • Our results revealed that aerobic exercise training (AET) was responsible for an improvement in body weight control, stimulate oxidative metabolism and nonenzymatic antioxidant activity associated with an increase in the expression of gene related to mitochondrial biogenesis in the liver of ob/ob mice with NAFLD

  • Variables related to AET were analyzed to determine trainability that means the adaptability of responses related to physical exercise

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Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of intrahepatic lipids, reaching an absolute level of 5% of the total hepatic content [1, 2]. This pathological process is associated with etiologic factors and metabolic comorbidities, such as insulin resistance (IR), cardiovascular diseases (CVD), and type 2 diabetes (T2DM), and is responsible for the progression of clinical staging for non-alcoholic steatohepatitis (NASH), liver cirrhosis and hepatocellular carcinoma (HCC) [3]. Part of the processes involved in the hepatic metabolic response is regulated by the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-a) and its signaling pathway and have important repercussions for lipid and glucose metabolism control, mainly in the stabilization of energy deficits in the liver and in the whole organism that are triggered by overweight and obese phenotypes and NAFLD [6]

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