Role of anethole dithiolethione regulating liver lipid metabolism, oxidative and ER stress in NAFLD: Insights from a mouse model

In preliminary studies, Anethole Dithiolethione (ADT) has exhibited significant potential in regulating mitochondrial fusion protein (Mfn) and mitigating the buildup of reactive oxygen species (ROS) in relation to NAFLD. This study aimed to explore the distinct role of ADT in the context of NAFLD by employing a mouse model. The C57BL/6J mice were divided into four groups: a regular diet group, a high-fat diet (HFD) group, and two groups receiving HFD supplemented with either 10 or 30 mg/kg ADT. Pathological changes were assessed through oil red O and hematoxylin-eosin staining. Lipidomics profiling was conducted to ascertain the composition of phospholipids, and RT-PCR along with WB were employed to analyze gene and protein expression pertinent to liver phospholipid transport, endoplasmic reticulum (ER) stress and lipid synthesis. The findings indicated that ADT elevated the levels of phospholipid components such as phosphatidylserine (PS) and phosphatidylethanolamine (PE), along with the upregulation of genes associated with liver lipid metabolism and endoplasmic reticulum (ER) stress (Mfn2, ATF6, PTDSS1, PTDSS2 and PPAR?). ADT also demonstrated the ability to decrease levels of liver inflammatory indicators and oxidative stress induced by the HFD, including ALT, AST, IL-6, TNF-?, MDA and catalase. These findings imply that ADT may serve as a promising therapeutic intervention for NAFLD by regulating Mfn2 expression and promoting PS transfer.