Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common disease that causes serious liver damage. Exercise is recognized as a non-pharmacological tool to improve the pathology of NAFLD. However, the antioxidative effects and mechanisms by which exercise ameliorates NAFLD remain unclear. The present study conducted exercise training on zebrafish during a 12-week high-fat feeding period to study the antioxidant effect of exercise on the liver. We found that swimming exercise decreased lipid accumulation and improved pathological changes in the liver of high-fat diet-fed zebrafish. Moreover, swimming alleviated NOX4-derived reactive oxygen species (ROS) overproduction and reduced methanedicarboxylic aldehyde (MDA) levels. We also examined the anti-apoptotic effects of swimming and found that it increased the expression of antiapoptotic factor bcl2 and decreased the expression of genes associated with apoptosis (caspase3, bax). Mechanistically, swimming intervention activated SIRT1/AMPK signaling-mediated lipid metabolism and inflammation as well as enhanced AKT and NRF2 activation and upregulated downstream antioxidant genes. In summary, exercise attenuates pathological changes in the liver induced by high-fat diets. The underlying mechanisms might be related to NRF2 and mediated by SIRT1/AMPK signaling.
Highlights
In the present study, we established a zebrafish high-fat diet (HFD) Nonalcoholic fatty liver disease (NAFLD) model and exercised the HFD zebrafish to explore the role of SIRT1/AMPK/Nuclear factor erythroid-2-related factor 2 (NRF2) signaling in the observed beneficial effects of exercise
Oil Red O staining revealed that HFD zebrafish livers had more lipid droplets than normal diet (ND) zebrafish livers, and that the high-fat diet plus exercise (HEX) group had fewer lipid drops than the HFD group (Figure 1C,D)
The HEX group had improved fasting blood glucose, liver triglyceride, and cholesterol levels compared to the HFD group (Figure 1E–G)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Because of the similar hepatic cellular composition, function, signaling, response to injury, and cellular processes that regulate liver disease between humans and zebrafish, zebrafish have been used to explore liver diseases, liver cancer, and regeneration [28] Due to their vigorous swimming capability, researchers have established swimming tunnel systems in zebrafish models for studying exercise physiology [29]. In the present study, we established a zebrafish high-fat diet (HFD) NAFLD model and exercised the HFD zebrafish to explore the role of SIRT1/AMPK/NRF2 signaling in the observed beneficial effects of exercise. These findings could form the basis of a novel complementary therapeutic strategy for NAFLD, which could prevent the development of more serious disease pathology
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
