The effect of hypoxia and normoxia training on autophagy in male rats hepatocytes with a high-fat diet

Degradation of autophagy is associated with hepatic fat accumulation. Although the increase in autophagy flux through diet, exercise, and hypoxia effectively improves the fatty liver, its molecular mechanisms are unknown. This study aimed to investigate the effect of nutrition and exercise on hypoxia and normoxia on liver autophagy.

Twenty-four male Wistar rats (weight=165±9 grams) were randomly divided into the normal diet (ND), high-fat diet (HFD), high-fat diet+ normoxia exercise (HFD+NE), and high-fat diet+ hypoxia exercise (HFD+HE). The exercise was performed in three weekly sessions for 12 weeks at 68 to 80 percent of maximal aerobic velocity in normoxia (high about 50 meters) and hypoxic-hypobaric (high about 3000  meters). In the end, tissue samples were collected to measure the liver fat content and Atg5 and Ulk1 gene expression changes. Data were analyzed using ANOVA tests (p<0.05).

Compared to the ND group, liver fat increased in the HFD group, and the expression of Atg5 and Ulk1 decreased (p<0.05). The increased liver fat in the training groups was lower than in the HFD group (p<0.05). Although exercise reduces decreasing expression of Atg5 caused by the high-fat diet, it was not significant. Ulk1 was higher in the HFD+HE group than in all groups (p<0.05).

The regulation of autophagy genes by exercise is probably an effective mechanism in preventing liver fat accumulation. Although hypoxia training had a more significant effect on the autophagy genes, it had not an additional effect on reducing liver fat content.