Hepatic gene expression in mouse models of non-alcoholic fatty liver disease after acute exercise

Aim: Non-alcoholic fatty liver disease (NAFLD) patients benefit from physical exercise. This study aimed to investigate the effect of acute exercise on hepatic gene expression in different mouse models of NAFLD.

Methods: C57BL/6J mice were fed with a control (CD) or a high fat (HFD) diet. AlbCrePten^flox/flox (Pten-KO) and Fxr^-/- mice, two genetic models of NAFLD with insulin hypersensitivity and resistance, respectively, were fed with CD. After 4 weeks, mice were randomly assigned to exercise or sedentariness. Mice were killed 15 min or 3 h after the running/sedentary period. Genome-wide hepatic gene expression was evaluated with the Illumina Micro-array platform. Quantitative polymerase chain reaction confirmed changes in gene expression.

Results: Acute exercise transiently affected the expression of genes involved in the immune response in C57BL/6 mice fed with CD and this effect normalized in the recovery phase. Acute exercise affected genes involved in gluconeogenesis in the insulin resistant Fxr^-/- model. Genes involved in lipid metabolism were affected in C57BL/6 mice fed with CD, but not in mouse models of NAFLD. Genes involved in DNA damage response pathways were deregulated only in C57BL/6 mice fed with CD and not in mouse models of NAFLD.

Conclusion: The simultaneous analysis of different NAFLD models revealed that an acute exercise bout affects hepatic gene expression differentially according to animal models and that most of the differentially expressed genes are involved in glucose and fatty acid metabolism, immune regulation, and DNA damage response.