α‐lipoic acid prevents non‐alcoholic fatty liver disease in OLETF rats

Abstract Background Insulin resistance, oxidative stress, inflammation and innate immune system activation contribute to the development of non‐alcoholic fatty liver disease ( NAFLD ) through steatosis and inflammation in the liver. The powerful antioxidant α‐lipoic acid ( ALA ) has been shown to improve insulin sensitivity and suppress inflammatory responses. This study explores how ALA administration protects against NAFLD . Methods Otsuka Long‐Evans Tokushima Fatty ( OLETF ) rats were divided into two groups (treated with 200 mg/kg/day of ALA or untreated) at 12 weeks of age and sacrificed at 28 weeks of age. Results Serum levels of insulin, free fatty acids, total cholesterol, triglyceride, leptin, IL ‐6 and blood glucose were decreased in ALA ‐treated rats. Serum adiponectin levels were higher in ALA ‐treated rats. ALA treatment decreased the expression of sterol regulatory element binding protein‐1 and acetyl CoA carboxylase, and increased glucose transporter‐4 expression in the livers of OLETF rats. Expression of the antioxidant enzymes heme oxygenase‐1 and Cu/Zn‐superoxide dismutase was increased in the livers of ALA ‐treated rats. The lipid peroxidation marker 4‐hydroxynonenal was decreased in the liver of ALA ‐treated rats. Proteins associated with innate immune activation (Toll‐like receptor‐4 and high‐mobility group protein box‐1) and inflammatory markers (vascular cell adhesion molecule‐1, intercellular adhesion molecule‐1, and cyclooxygenase‐2) were decreased in the livers of ALA ‐treated rats. Conclusions Chronic ALA supplementation prevents NAFLD through multiple mechanisms by reducing steatosis, oxidative stress, immune activation and inflammation in the liver.