Experimental Study On The Mechanism Of Nonalcoholic Fatty Liver Disease And Insulin Resistance In Rats Induced By Different Oils

It has been demonstrated that inappropriate or excessive intake of oil increased free fatty acids(FFA)in body and ultimately results in disturbance of lipid metabolism and insulin resistance(IR)as well as nonalcoholic fatty liver disease(NAFLD).The performances are different due to the diverse proportions of fatty acids in distinct oils.The NAFLD and IR in rats induced by different oils(lard and palm oil riched in saturated fatty acids,olive and camellia seeds oil riched in unsaturated fatty acids)were compared and the mechanisms were studied in this paper.Method:35 male SD rats(70±10g)in SPF grade were randomly divided into five groups(N=7).Rats in control group were fed a standard chow diet a nd rats in model groups were fed high fat diet containing different oils(lard,palm oil,olive and camellia seeds oil).Each group was given freedom food a nd water.Body weight was measured weekly for 17 weeks.In the end of 17th week,abdominal circumferences and heights were measured.Then Oral glucos e tolerance test(OGTT)and insulin tolerance(ITT)test were performed.The artery blood samples were collected after anesthesia,then serum and plasma were separarted.The weight of liver and abdominal adipose were recorded.Then the obesity index(Lee's index,liver index and the proportion of body fat)were calculated.Liver biopsy was fixed in formalin and embedded in paraffin for HE st aining.The levels of fasting serum lipids(TC,TG,LDL-C,HDL-C),fasting plas ma glucose(FPG),oxidation stress(SOD,MDA,LPO),liver function(AST,AL T)were tested.Fasting serum insulin(FIN),adiponectin and leptin were detect ed by ELISA kits,and the insulin resistance index(HOMA-IR)was calculated.The composition of FFAs in livers were measured with GC/MS.The gene of lipid synthesis,lipolysis,glucose metabolism and insulin signaling in liver wer e analyzed by real time PCR.Results:1.After 17 weeks,high-fat diet groups exhibited significantly increased in body weight,fat and Lee's index.The rats in lard-fed group revealed marked hyperlipemia,followed by the palm oil group.There was no significant change in the serum lipids of the camellia seed oil and olive oil diet groups and it showed no difference between camellia seed oil and the control group.2.Each oil-fed group showed different levels of IR.Lard and palm oil-fed groups led to the obvious IR,as exemplified by increased level of FPQ FINS and HOMA-IR,impaired OGTT and ITT performance.The level of serum adiponectin was decreased and leptin level was increased.There were also differences in the expression in glucose metabolism and insulin signaling gene.PEPCK and FOXO1 were highly expressed in livers of lard and palm oil-fed rats while olive oil and camellia seed oil-fed groups showed little difference compared with the normal groups.The expressions of G6P increased in each oil fed group,among them all,lard and palm oil-fed groups distinctly exceeded other groups while ChREBP was significantly higher in lard group than other groups.The expression of IRS2 and INSR genes decreased in lard and palm oil-fed rats.The IR in camellia seed oil and olive oil fed-rats were slighter,and the gene of glucose metabolism and insulin signaling were ameliorated compared with lard group.3.The high-fat diet induced significant disturbance of lipid metabolism in lard and palm oil groups and exhibited severe hepatic steatosis.While oil groups(olive oil,camellia seed oil)which have main components of monounsaturated fat exhibited slighter hepatic steatosis.The expressions of lipid metabolism-related genes in liver also revealed differences in diverse groups.Lipid synthesis genes includs FAS,SCD1,ACC1,GPAT and DGAT2.Among them,ACC1,GPAT and DGAT2 in lard and palm oil groups were highly expressed.While the camellia seed oil and olive oil-fed groups differed inconspicuously with normal groups.The expression of SCD1 increased a little in lard and palm oil-fed groups while the other two groups remained almost the same with normal groups.FAS in every oil-fed group all expressed a high standard,but the camellia seed oil-fed group showed a lower standard.Lipolysis gene contains PPARa,ACOX1 and CPT1.PPAR a and ACOX1 significantly decreased in lard and palm oil groups,while other groups showed little difference.The level of CPT1 in each oil-fed group all declined with the lard group as the lowest.Conclusion:Due to the different composition of fatty acids,the degree of IR and hepatic steatosis induced by diverse oils were distinct.High SFA diet induced significant disturbance of lipid metabolism,IR and serious NAFLD.While high UFA diet with appropriate ratio of n6/n3 improved the above symptoms.The mechanism of NAFLD is:The increased FFA and obesity induced by high fat diet lead to IR and then cause hepatic steatosis.FFA causes toxicity by increasing oxidative stress and by activation of inflammatory pathways,and finally leads to liver cell damage and NAFLD.