The Investigations Of Zinc-α2-Glycoprotein In The Improvement Of Hepatic TG Accumulation Through Farnesoid X Receptor

Objective: To investigate whether Zinc α2 glycoprotein(ZAG)can improve hepatic TG accumulation by activating Farnesoid X receptor(FXR).Methods:Aged 8 weeks Wild type(WT)and FXR heterozygote male C57BL/6 mice(WT/KO)With litter born primary hepatocytes were isolated with collagenase perfusion.The primary hepatocytes were treated with palmitic acid for 24 h in order to establish the model of fat deposition in the hepatocytes.Then the primary hepatocytes were divided into 4 groups after transfected by Ad-ZAG,which were(1)WT;(2)WT+Ad-ZAG;(3)WT/KO;(4)WT/KO+Ad-ZAG group.The hepatocytes in WT+Ad-ZAG and WT/KO+Ad-ZAG group were transfected with Ad-ZAG.After 48 hours,Oil Red O staining was used to observe the intracellular lipid droplets,and intracellular triglyceride content was detected by Enzymatic method.The protein expressiom level of ZAG,metabolic nuclear receptors(SREBP-1c)and(FAS)were detected by Western blot.Results:1.After treated with palmitic acid,less orange lipid droplet and decreased intracellular triglyceride content(P<0.01)were observed in WT+Ad-ZAG cells when compared with the WT group.However,there were no significant differences in orange lipid droplet and intracellular triglyceride concent in WT/KO+Ad-ZAG hepatocytes compared with the WT/KO group.2.Compared with WT group,the protein level of ZAG was increased in WT+Ad-ZAG(P<0.01),While the protein level of SREBP-1c,FAS were significantly decreased(P<0.05);In WT/KO+Ad-ZAG group,the protein level of ZAG was notablely upregulated(P<0.01).But the protein level of SREBP-1c,FAS were not decreased significantly compared with WT/KO group(P>0.05).Conclusion: ZAG might improve hepatic TG accumulation by activating FXR.