Folic Acid Combined with Melatonin Might Prevent Hepatic Steatosis by Alleviating Endoplasmic Reticulum Stress to Promote Lipid Droplet Lipolysis in High-Fat Diet-Fed Mice

<b>Objectives</b>: The purpose of this study is to observe the preventive effect of folic acid (FA) combined with melatonin (MLT) on high-fat diet (HFD)-induced hepatic steatosis and to explore its potential mechanism. <b>Methods</b>: Fifty male C57BL/6J mice were randomized into five groups: control group (CN), high-fat diet group (HD), FA supplementation group (HF), MLT supplementation group (HM), and FA combined with MLT supplementation group (HFM). The experiment lasted for 10 weeks. <b>Results</b>: FA combined with MLT effectively inhibited HFD-induced increases in liver index, hepatic TG levels, and serum TG levels. Histological examination revealed that FA combined with MLT significantly reduced the area of hepatic steatosis and the accumulation of lipid droplets (LD). Western blot analysis showed FA combined with MLT activated AMPK, inhibiting the expression of ERS-related proteins, thereby reducing the expression of LD lipolysis-associated proteins. <b>Conclusions</b>: FA combined with MLT might prevent HFD-induced hepatic steatosis by attenuating ERS and subsequently promoting LD lipolysis.