sitosterol attenuates high- fat diet-induced hepatic steatosis in rats by modulating lipid metabolism, inflammation and ER stress pathway

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disorder. The naturally occurring phytosterol; [beta]-sitosterol has antiobesogenic and anti-diabetic properties. The purpose of this study was to explore the role of [beta]-sitosterol in preventing hepatic steatosis induced by a high-fat diet (HFD) in rats. In the current study, to induce NAFLD in the female Wister rats, an HFD was administered to them for 8 weeks. The pathogenic severity of steatosis in rats receiving an HFD diet was dramatically decreased by oral administration of [beta]-sitosterol. After administering [beta]-sitosterol to HFD-induced steatosis for three weeks, several oxidative stress-related markers were then assessed. We showed that [beta]-sitosterol reduced steatosis and the serum levels of triglycerides, transaminases (ALT and AST) and inflammatory markers (IL-1[beta] and iNOS) compared to HFD-fed rats. Additionally, [beta]-sitosterol reduced endoplasmic reticulum stress by preventing the overexpression of inositol-requiring enzyme-1 (IRE-1[alpha]), X-box binding protein 1(sXBP1) and C/EBP homologous protein (CHOP) genes which, showing a function in the homeostatic regulation of protein folding. Also, it was found that the expression of the lipogenic factors; peroxisome proliferator-activated receptor (PPAR-[alpha]), sterol regulatory element binding protein (SREBP-1c) and carnitine palmitoyltransferase-1(CPT-1), which are involved in the regulation of the fatty acid oxidation process, may be regulated by [beta]-sitosterol. It can be concluded that [beta]-sitosterol may prevent NAFLD by reducing oxidative stress, endoplasmic reticulum stress and inflammatory responses, which supports the possibility of using [beta]-sitosterol as an alternative therapy for NAFLD. Together, [beta]-sitosterol may be an option for NAFLD prevention. Keywords: NAFLD, [beta]-sitosterol, Endoplasmic reticulum stress, PPAR-[alpha], SREBP-1c, CPT-1