DJ-1 protein ameliorates nonalcoholic fatty liver disease via ER-stress pathway and reduces inflammation.

Originally identified in Parkinson's disease (PD), DJ-1 is a multifunctional protein increasingly recognized for its role in gastrointestinal and hepatic disorders. This study aimed to elucidate the potential mechanisms of DJ-1 in Nonalcoholic fatty liver disease (NAFLD), which is the early stage of various hepatic disorders. We examined the effects of DJ-1 protein in high-fat diet (HFD) and methionine-choline deficient diet (MCD) feeding mice. NAFLD cell model was induced using three different liver-derived cell lines with palmitic acid (PA) to identify the mechanistic role of DJ-1. DJ-1 expression is reduced in NAFLD mouse model. The protective effect of DJ-1 against lipid accumulation is associated with ER-stress pathway in DJ-1-silenced cells and DJ-1 overexpression conditions. Furthermore, DJ-1 alleviated inflammation in PA-induced NAFLD cells. Overall, DJ-1 could be a promising therapeutic target due to its protective role against steatosis in NAFLD, which is linked to ER stress and cellular inflammation, potentially preventing the progression of NAFLD to more advanced hepatic disorders.