Changes And Effects Of FGF21/AMPK/ACC Pathway On Hepatic Triglyceride Deposition In Hyperglycemic Rats Induced By Partial Pancreatectomy

Objective:To investigate the role of FGF21/AMPK/ACC pathway in hepatic triglyceride deposition induced by partial pancreatectomy in hyperglycemic rats.Methods:Forty male SD rats were randomly divided into normal group(group Ⅰ),sham operation group(group Ⅱ),operation group(group Ⅲ)and operation + intervention group(group Ⅳ),with 10 rats in each group(n=10).All rats were fed under the same conditions.Group I was the normal control group without any treatment;Group Ⅱ was only splenectomy after laparotomy;Group Ⅲ and Ⅳ were treated with partial splenectomy and pancreas after laparotomy;and Group Ⅳ was additionally given insulin intervention(insulin glargine injection,0.1U/kg,once a day,subcutaneously)on the basis of Group Ⅲ.Fasting blood glucose was measured in each group before and 24 h after surgery,respectively.C-peptide release test was performed 4 weeks after surgery,and insulin release test was performed in groups I,Ⅱ and Ⅲ 4 weeks after surgery.The weight of rats in each group was measured before and 4 weeks after surgery.At the end of 4 weeks,heart blood was collected and serum samples were centrifuged to determine the concentration of FGF21.Complete liver tissue was collected and TG content was measured by glycerol phosphate oxidase(GPO-PAP).Immunohistochemistry was used to observe and compare the positive expressions of p-AMPK,AMPK,p-ACC and ACC in liver tissue of rats in each group,and the levels of p-AMPK/AMPK and p-ACC/ACC in liver tissue of rats in each group were analyzed and compared by Image J software.Results:1.There was no significant difference in preoperative fasting blood glucose among all groups(P>0.05).Fasting blood glucose at 24 hours after operation: there was no significant difference between group Ⅰ and group Ⅱ(P > 0.05),and there was significant increase between group Ⅲ and group Ⅱ(P < 0.05).There was no obvious difference between group Ⅳ and group Ⅲ(P > 0.05).Four weeks after operation,insulin release test was performed on rats in groups Ⅰ,Ⅱ and Ⅲ,and the results showed that there was no significant difference in insulin concentration at 0h,0.5h,1h and 2h between group Ⅰ and group Ⅱ(P > 0.05).Compared with group Ⅱ,there was no significant difference in 0h insulin concentration of group Ⅲ(P > 0.05),and the concentrations of 0.5h and 1h insulin were significantly decreased(P < 0.05).There was no significant difference in 2h insulin concentration of group Ⅲ.Four weeks after operation,C-peptide release test was performed in each group.The results showed that there was no significant difference in 0h,0.5h,1h and 2h C peptide concentrations between groups Ⅰ and Ⅱ(P>0.05).Compared with group Ⅱ,there was no obvious difference in 0hC peptide concentration in group Ⅲ(P > 0.05),and the concentration of 1hC peptide at 0.5h was significantly decreased(P <0.05),and there was no significant difference in 2hC peptide concentration(P > 0.05).Compared with group Ⅲ,there were no significant differences in 0h,0.5h,1h and 2HC peptide concentrations in group Ⅳ(P>0.05).2.There was no obvious distinction in liver TG content between group I and group Ⅱ(P>0.05).Compared with group Ⅱ,liver TG content of group Ⅲ was significantly increased(P<0.05),and liver TG content of group Ⅳ was significantly decreased compared with group Ⅲ(P < 0.05).3.There was no obvious distinction in serum FGF21 concentration between groups I and Ⅱ(P > 0.05).The serum FGF21 concentration in group Ⅲ was obviously lower than that in group Ⅱ(P < 0.05),and the serum FGF21 concentration in group Ⅳ was significantly higher than that in group Ⅲ(P < 0.05).4.The levels of p-AMPK/AMPK and p-ACC/ACC in liver of rats in group Ⅲ were significantly lower than those in group Ⅱ,and the levels of p-AMPK/AMPK and p-ACC/ACC in liver of rats in group Ⅳ were significantly higher than those in group Ⅲ.Conclusion:In hyperglycemic rats induced by partial pancreatectomy,serum FGF21 concentration was significantly decreased and liver triglyceride deposition was significantly increased.After insulin hypoglycemic treatment,serum FGF21 concentration was significantly increased,liver triglyceride deposition was significantly decreased,and fatty liver was significantly improved.The levels of p-AMPK/AMPK and p-ACC/ACC in liver tissue of rats with elevated liver triglyceride were significantly lower than those of the sham operation group,and the levels of p-AMPK/AMPK and p-ACC/ACC were significantly higher after insulin intervention than those of the operation group.