Liver macrophages mediate effects of downhill running and caloric restriction on nonalcoholic fatty liver disease of high fat diet-fed mice

Abstract

Aims: The mechanism of physical activity and calorie restriction remedying non-alcoholic fatty liver disease (NAFLD) remains elusive. The purpose of this study is to explore the effects of eccentric exercise and dietary regulation allied or alone on high-fat diet (HFD) induced NAFLD and its potential mechanism.

Materials and methods: Mice were fed with HFD for 12 weeks and subsequently treated with chronic downhill running and caloric restriction for 8 weeks. Related biochemical index were examined both before and during intervention to evaluate the liver injury and dyslipidemia. Levels of MCP1, TNFα, IL-1β, IL-6 and IL-10 were detected by ELISA. Liver morphology was observed by H&E and oil red O staining. Protein contents of iNOS, Arg-1, IL-1β and IL-10 were determined by Western blot. CD86 and CD206 fluorescence were determined by Immunofluorescence. KEY FINDING: (1) 12 weeks' HFD induced hyperlipemia and hepatic steatosis by activating M1 macrophages phenotype and inhibiting M2 macrophages. (2) Chronic downhill running and caloric restriction promoted liver M2 macrophages phenotype, and inhibited M1 macrophages, to attenuate chronic inflammation and ameliorate hepatic steatosis. (3) The effects of downhill running and dietary regulation allied were more effective on improving NAFLD compared with downhill running or caloric restriction alone.

Significance: Eccentric exercise accompanied by caloric restriction attenuates HFD-related NAFLD by promoting M2 macrophages phenotype and inhibiting M1 macrophages in liver. These findings may be help to designing better non-pharmacological intervention programs for NAFLD patients.

Keywords: Caloric restriction; Chronic inflammation; Downhill running; Macrophage polarization; NAFLD.