| Objective The choice of dietary oil is closely related to the pathological process of alcoholic fatty liver disease(AFLD).This study used corn oil rich in n-6 polyunsaturated fatty acids(PUFAs)as a control group to evaluate the effect of olive oil(OO)rich in monounsaturated fatty acids(MUFAs)on the pathological process of alcoholic fatty liver disease and initially reveal its underlying mechanism.Methods C57BL/6J mice(male,8-week-old)were employed in this study.Twenty experimental mice were randomly divided into four groups,namely corn oil control feed group,corn oil alcohol feed group,olive oil control feed group,olive oil alcohol feed group,and olive oil alcohol feed group.Lieber-DeCarli liquid alcohol feed was fed for 4 weeks to establish the AFLD model.Biochemical kits were used to detect the levels of liver function,blood lipids,intrahepatic lipids,etc.Quantitative real-time PCR(qRT-PCR),western blotting and other molecular biological methods were used to evaluate the effect of MUFAs-rich olive oil on the pathological process of AFLD and reveal its underlying mechanism.Results Histology and biochemical parameters proved that dietary olive oil significantly aggravated alcohol-induced liver dysfunction in mice.Compared with the corn oil alcohol feed group,the olive oil alcohol feed group significantly increased the levels of cholesterol(TC),triglyceride(TG)and free fatty acid(FFA)in liver(P<0.05).Increased tevels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),TC,TG,and low-density lipoprotein cholesterol(LDL-C)in plasma(P<0.05);Exacerbates the state of oxidative stress in liver,mainly manifested by an increase in the level of malondialdehyde(MDA)in liver(P<0.05).Western blot analysis and qRT-PCR showed that dietary olive oil significantly aggravated alcohol-induced liver lipid accumulation and inflammation in mice.Mechanistic studies have shown that compared with the corn oil alcohol feed group,the protein expression of hormone-sensitive lipase(HSL),phosphorylated 5’-amp-activated protein kinase(p-AMPK),carnitine palmitoyl transferase-Ⅰα(CPT1α)was significantly reduced in the olive oil alcohol feed group(P<0.05).The protein expression of sterol regulatory element-binding protein-1c(SREBP-1c),diacylglycerol acyltransferase-2(DGAT2),and very low-density lipoprotein receptor,VLDLR)was significantly increased in the olive oil alcohol feed group(P<0.05).It also promotes the expression of fatty acid synthesis factors including fatty acid synthase(FAS),stearoyl-CoA desaturase I(SCD-1)(P<0.05)at the transcription level,and pro-inflammatory factors including hepatic interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)(P<0.05).In addition,dietary olive oil also promoted alcohol-induced lipolysis of adipose tissue in mice,thereby aggravating hepatic steatosis.Conclusion Compared to corn oil,MUFAs-enriched olive oil significantly exacerbated alcohol-induced liver dysfunction in mice.Olive oil regulates genes,proteins associated with liver lipid synthesis and metabolism,pro-inflammatory factors,and increases the breakdown of adipose tissue.It may be one of the underlying molecular mechanisms leading to liver dysfunction. |