High-intensity interval training can inhibit of PPARγ/ OSBPL3 pathway through epigenetic alterations in Non-Alcoholic Fatty Liver Disease

Abstract

Objectives: Although previous reports show that high-intensity interval training (HIIT) can provide positive effects on NAFLD, However, the mechanism of these effects has not been well demonstrated. On other hands, new findings showed PPARγ/ OSBPL3 pathway could be an important target for the treatment of NAFLD, therefore in this study we investigated the possible effect of HIIT on PPARγ/ OSBPL3 pathway through DNMTs gene expression and activity.

Methods: 30 adult male wistar rats were divided into three groups including normal diet sedentary (ND-SED), high-fat diet sedentary (HFD-SED), high-fat diet & high-intensity interval training (HFD+HIIT), high-fat diet. Firstly, in order to induce fatty liver, high-fat food was used for 12 weeks. Blood samples were collected to determine serum levels of glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lipid profile the extracted livers were used for biochemical assays and real time PCR studies. DNMT1, DNMT3A, and DNMT3B activities were assessed in hepatic tissue.

Results: HFD administration significantly increases serum TC, TG and LDL levels (all p < 0.001). It also, increases AST and ALP activity, these effects were ameliorated by HIIT treatment. Compared with the ND-SED group, the HFD-SED group showed significantly increased expression and activity of DNMT1, DNMT3A and DNMT3B (P < 0.01) and also significantly increased expression of PPARγ and OSBPL3 (P < 0.01) in liver tissue. The expression and activity of DNMTs were significantly decreased in HFD+HIIT compared to HFD -SED rats. There were positive significant correction between PPARγ and OSBPL3 with DNMTs activity and gene expression.

Conclusion: HIIT may be helpful in the prevention of NAFLD by modulating some serum liver function markers, lipid profile and glycemic status. In addition, HIIT can inhibit the development of NAFLD by reducing the expression of PPARγ and OSBPL3 through reducing activity and expression of DNMTs.