Nonalcoholic fatty liver disease (NAFLD) is a kind of serious fat disorder that has become a critical problem to human society. Therefore, finding drugs that are safe and effective has become more and more important. Erythritol (Ery) is a polyol sweetener with a variety of biological functions. However, whether Ery has a relieving effect on NAFLD has not been reported yet. Therefore, we induced HepG2 cells with oleic acid and palmitic acid as our in vitro model. Moreover, we choose wild-type mice with tyloxapol and high-fat diet and nuclear factor E2-related factor 2 (Nrf2) knockout mice with high-fat diet as our in vivo model. We found that Ery could reverse the lipid accumulation, oxidative stress, and endoplasmic reticulum stress caused by the NAFLD model. The mechanism studies showed that Ery promoted the translocation of Nrf2 from cytoplasm to nucleus, and the molecular simulation docking results of Ery and Nrf2 showed that there was a hydrogen bond between them. Moreover, Ery could promote the production of HO-1 and NQO1 antioxidant proteins and inhibit the expression of endoplasmic reticulum stress proteins GPR78, p-PERK, and CHOP. On the contrast, when Nrf2 was knocked out in mice, Ery lost its protective effect on NAFLD. In conclusion, we found that the potential mechanism of Ery's protective effect is that it plays an antioxidant role by activating the Nrf2 signaling pathway, thereby inhibiting endoplasmic reticulum stress and lipid accumulation in NAFLD.
Keywords: HFD; endoplasmic reticulum stress; lipid accumulation; oleic acid; palmitic acid; tyloxapol.