Gavin Fredrickson

Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology ranging from fatty liver to non-alcoholic steatohepatitis (NASH), which is characterized by steatosis, inflammation, hepatocellular injury, and fibrosis. Notably, immune cell-driven inflammation is a significant mechanism in the transition from fatty liver to the more serious NASH. In humans and animal models, physical exercise ameliorates the progression of NAFLD, independently of changes in body-weight. However, the intensity of activity needed to induce an anti-inflammatory environment and improve NAFLD outcomes, as well as the underlying immune mechanisms by which exercise reduces inflammation in this disease, are unclear. We hypothesized that exercise of high intensity is superior in dampening the inflammatory process of NAFLD, compared with an isocaloric, moderate-intensity exercise modality. We fed 5-week-old wildtype mice a high-fat-high-carbohydrate (HFHC) diet for 6 weeks to induce NAFLD. Mice were then left sedentary (SED) or assigned to either a moderate-intensity training (MIT) or high-intensity interval training (HIIT) exercise regimen for an additional 12 weeks. Compared with the SED group, both MIT and HIIT resulted in decreased body-weight and adiposity, as well as improved metabolic and inflammatory tone. Despite no differences in body-weight, HIIT exercise resulted in decreased adiposity, lower liver weight, and improved glucose and insulin tolerance, compared with the MIT group. These improvements in NAFLD were associated with decreased infiltration of pro-inflammatory monocytes and macrophages. These findings suggest that exercise of high intensity is superior in ameliorating the progression of NAFLD via body weight-independent improvements in metabolism and macrophage-driven inflammation.