N-3 PUFAs Regulated Liver Injury By Adiponectin In High Fat Induced ApoE^-/- Mice

Objective:To investigate the protective effect of different ratios of DHA / EPA to liver injury and the adjustment mechanism of adiponectin in liver in Apo E-/- mice.Methods:1.Ninety male Apo E-/- mice and fifteen male wild type C57BL/6J mice were randomly divided into seven groups:group CT:C57BL/6J mice(Normal diet,distilled water),group ND: Apo E-/- mice(Normal diet,distilled water),group HFD: Apo E-/-mice(HFD,distilled water),group ALA:Apo E-/-mice(HFD,ALA1mg/g bw),group DHA/EPA=2∶1 : Apo E-/-mice(HFD, DHA/EPA=2∶1, 1mg/g bw), group DHA/EPA=1∶1 : Apo E-/-mice(HFD, DHA/EPA=1∶1, 1mg/g bw), group DHA/EPA=1∶2: Apo E-/-mice(HFD,DHA/EPA=1∶2,1mg/g bw).2.After 12 weeks feeding,killed mice,collected blood samples and recorded body weight of mice,and calculate the organ index.Determination of lipid levels in mice( TC and TG of serum,TC and TG of liver tissues),serum enzyme activity(AST,ALT,AKP) and liver oxidative damage(MDA,SOD,GSH).Producted liver biopsy and observed liver injury by HE staining and electron microscopy.Detected serum adiponectin level in Apo E-/- mice by Elisa. Making immunohistochemical analysis to adiponectin and Adipo R2; Determination of liver adiponectin and adiponectin receptors(Adipo R1 and Adipo R2)、peroxisome proliferator-activated receptor γ(PPARγ) mRNA expression levels; Using western blot to analysis liver protein of adiponectin.Results:1.The results showed that,compared with the ND group,HFD group body weight,food intake,liver organ index of Apo E-/- mice increased significantly(p<0.05),and intervention group body weight,food intake volume,liver index of Apo E-/- mice slightly higher than ND group,but no statistically significant.Intervention group body weight,food intake of ApoE-/- mice in liver have no significant differences compared with HFD group.HFD group have more fat degeneration in liver cells observed by HE staining and electron microscopy,and each group lipid accumulation decreased and liver cells lipid infiltration was improved intervened by DHA/EPA.2.Compared with the ND group,TC and TG content of liver and serum,serum AST and ALT and AKP levels, liver SOD levels were significantly increased in HFD group(p<0.05),and SOD levels were no significant differences(p>0.05),and liver GSH levels were significantly decreased(p<0.05).After the DHA / EPA intervention,compared with the HFD group,TC and TG content of serum and liver,AST and ALT and AKP levels of serum,and MDA levels of liver were significantly decreased(p <0.05),SOD and GSH levels were significantly increased(p <0.05).3.Compared with the ND group,HFD group serum adiponectin levels in Apo E-/- mice was significantly lower(p <0.05);Compared with the HFD group,DHA/EPA intervened group serum adiponectin levels were significantly higher(p<0.05).(p<0.05)Immunohistochemistry showed that,compared with the ND group,the lower adiponectin and Adipo R2 expression levels in HFD group,adiponectin and Adipo R2 levels were significantly increased in DHA/EPA intervened group.4.Compared with the HFD group,adiponectin,PPARγ,Adipo R1 and Adipo R2 mRNA expression levels have significant increase in DHA / EPA intervened group(p<0.05),and when DHA / EPA = 1∶2, adiponectin protein expression levels were significantly increased(p <0.05).Conclusions:DHA / EPA can significantly improve serum adiponectin levels,lipid levels,enzyme activity levels and oxidative damage levels in Apo E-/- mice,and DHA/EPA can improve liver lipid infiltration and alleviating liver injury.By adjusting adiponectin and related gene,DHA / EPA have a protective effect on liver injury.