Rhodiola activates macrophage migration inhibitory factor to alleviate non-alcoholic fatty liver disease

Rhodiola was found to be a potential treatment for nonalcoholic fatty liver disease (NAFLD). The macrophage migration inhibitory factor (MIF)-regulated lipophagy and lipid metabolism might be the therapeutic targets of Rhodiola. A 16-week high-fat diet (HFD) was used to simulate a NAFLD mouse model. Rhodiola extract or normal saline were administrated to mice. Blood was collected to assess blood glucose and insulin, and livers were harvested to assess lipid accumulation and metabolism. In cell experiments, the active ingredient of Rhodiola, salidroside, and recombinant MIF protein (rMIF) were used to treat palmitate (PA)-incubated HepG2 cells, with MIF-siRNA or NC-siRNA transfection. Then, the level of lipophagy and lipid metabolism was examined. Rhodiola improved lipid accumulation and metabolism disorder of HFD mice. The oil red O staining of the liver showed that increased lipid droplets in the NAFLD liver could be relieved by Rhodiola; Rhodiola also alleviated the increasing body weight, liver weight, and HOMA-IR index of HFD mice. Results in cell experiments were consistent: salidroside relieved the lipid droplet accumulation and triglyceride release in PA cells, as well as reduced lipophagosome and lipid metabolism disorder in PA cells. However, all these effects of salidroside were partially blocked by MIF-siRNA transfection. Rhodiola reduces lipid accumulation in the liver of NAFLD by facilitating the MIF pathway and the downstream lipophagy and lipid metabolism. MIF may be an endogenous regulator of liver lipophagy and lipid metabolism and a potential therapeutic target for NAFLD.