Sterol Ferulate Rich Wheat Bran Oil Concentrate Prevents Liver Damage in MAFLD Mouse Model by Modulating FAS and PCSK9

Molecular effects of sterol-enriched wheat bran oil (eWBA) on lipid metabolism, inflammatory markers, and liver proteome associated with nonalcoholic/metabolic-related fatty liver disease (MAFLD) are not completely known. In this study, dietary eWBA intervention was used to investigate its effect in ameliorating liver injury in high fat diet (HFC)-fed C57BL/6 mice. Specifically, we examined eWBA’s effects on (i) differentially expressed hepatic factors which regulate carbohydrate and lipid homeostasis markers, such as sterol regulatory element-binding protein-2 (SREBP-2), peroxisome proliferator-activated receptors-γ (PPARγ), pro-protein convertase subtilisin/kexin type-9 (PCSK9), low-density lipoprotein receptor (LDL-R), and apolipoprotein-E (APO-E) factors, and (ii) levels of two cytokines, tumor necrosis factor (TNF-α) and transforming growth factor beta (TGF-β). Liver of HFC-fed mice exhibited characteristic features of MAFLD, such as increased liver injury serum markers (SGOT, SGPT), liver lipids, and PCSK9 protein. Mice fed eWBA-supplemented HFC exhibited amelioration of serum cholesterol, triglycerides, SGOT, and SGPT levels as well as a reduction in liver lipids and PCSK9 and SREBP-2 proteins. Pro-inflammatory and pro-fibrogenic cytokines in the liver of the groups fed with eWBA - supplemented HFC were normalized with respect to the group without eWBA. To conclude, eWBA reduces the expression of SREBP-2, APO-E, and PCSK9 in the liver which down regulates various signal molecules thereby ameliorates liver injury in a mouse model of MAFLD. Down-regulated FAS and ZNF-236 of liver proteins with eWBA intervention could be the initial markers for steatosis.