Investigating the regulatory potential of interval training and IPA supplementation on modulating the hepatic gluconeogenesis pathway in rats with non-alcoholic fatty liver disease

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is closely linked to metabolic disturbances such as hyperglycemia, insulin resistance, and obesity, yet the mechanisms underlying impaired hepatic gluconeogenesis remain unclear. This study addresses this gap by examining how interval training and indole-3-propionic acid (IPA) supplementation regulate the hepatic gluconeogenesis pathway in a rat model of NAFLD. Materials and methods Twenty-five male Wistar rats were randomly assigned to five groups including, control, NAFLD, NAFLD + HIIT, NAFLD + IPA, NAFLD + HIIT + IPA. At the end of the experiment, lipid profile and changes FBS and insulin and HOMA-IR as well as insulin resistance were measured in serum, changes in liver weight and liver triglyceride, as well as FXR gene expression and G6Pase protein changes in the liver tissue of all rats. Oil-red O and H&E staining were used to measure the amount of fat deposition and histopathological changes in liver tissues. Results A high-fat diet containing fructose significantly increased lipid profile, insulin sensitive parameters, as well as liver enzymes (ALP, ALT, AST) in serum, and also increased the amount of G6Pase protein and decreased FXR gene was expressed in liver tissue. However, the interaction of 8-week HIIT and IPA supplementation resulted in a significant improvement of the mentioned biomarkers, with a significant decrease in G6Pase protein levels and an increase in FXR gene expression compared to obese rats with non-alcoholic fatty liver disease. Conclusion Based on the obtained results, it seems that the interaction of HIIT and IPA supplement consumption leads to the consumption of more circulating fuels, and at the same time, it causes a decrease in gluconeogenesis and the adjustment of blood sugar and liver status, and is probably effective in preventing the complications of obesity and non-alcoholic fatty liver.