Swimming prevents nonalcoholic fatty liver disease by reducing migration inhibitory factor through Akt suppression and autophagy activation.

Physical inactivity is an important contributor to obesity and fat accumulation in tissues. Critical complications of obesity include type II diabetes and nonalcoholic fatty liver disease (NAFLD). Exercise has been reported to exert ameliorating effects on obesity and NAFLD. However, the underlying mechanism is not fully understood. We showed the increase of microRNA-451 (miR-451) and decrease of macrophage migration inhibitory factor (MIF) in liver, after swim training in high fat diet (HFD) mice. MIF expression was regulated by miR-451. HFD intake caused the increase of body weights in WT and MIF knockout (KO) mice. In addition, HFD-induced liver anomalies were associated with Akt activation and autophagy suppression, which were reversed by MIF KO. In hepatocytes from HFD WT and MIF KO mice, autophagy was inhibited by exogenous rmMIF through Akt activation. Meanwhile, miR-451 antagonized the regulation of MIF on Akt signaling and autophagy. Taken together, these results indicate that MIF was decreased in liver of HFD mice due to physical exercise, and might prevent hepatic steatosis by suppressing Akt signaling and promoting autophagy.