Effects Of Liraglutide On Liver Tissue Of Obese Mice With Nonalcoholic Fatty Liver Disease

objective: establish the model of obese mice and diabetes obese mice andexplore the effects of Liraglutide on the level of body weight and glucose,insulin resistance, liver histologic pathology, adenylyl cyclase3.Methods: Twenty-four C57BL/6J mice and Sixteen db/db diabetes mice in4weeks of clean grade were purchased in the animal breeding center, C57BL/6Jmice were divided into A group (n=8), B group (n=8),C group (n=8) randomly.The A group mice were fed by normal diet. The B, C group mice were givenhigh-sugar and high-fat feed. Sixteen diabetes mice were divided into D group(n=8), E group (n=8). All mice were free access to water, at room temperaturecontrolled at18-22°C, relative humidity30%-70%. All groups of mice were fedmorning and evening twice a day, daily food in-take of every mouse was3%ofthe body weight. After feeding4weeks, Liraglutide was intervened in group Cand E,twice daily. group B and D was given normal saline by the way. bodyweight and blood glucose were measured weekly.After12-week’s intervention, the liver tissue was obtained and measured the expression of AC3mRNA byreal time quantitative polymerase chain reaction(RT-PCR). Liver histologicalexamination: paraffin sections, HE staining,Masson staining,Oil-red-O staining,light microscopy of liver pathology. Then the blood samples were centrifugedand plasma was assayed for insulin. The concentrations of insulinwere measured by using a RIA-kit. Compare body weight, blood glucose,FINS, insulin resistance index of each group. Observe theintracellular TG accumulation in liver. Investigate the relationshipbetween the cytosolic TG accumulation in liver and insulin resistance,body weight and expression of AC3mRNA. All results were measured by(x±s)， using SPSS19.0software package, multiple groups means werecompared with ONE WAY ANOVA, α=0.05. Count data were measured bynumber(n), compared with rank-sum test α=0.05.Result:1. liraglutide significantly promote obese mice and the diabetic obese miceAC3mRNA expression, decrease weight,improve blood glucose and insulinresistance (p<0.01). Liraglutide12-week’s treatment, db/db mice, theintervention group compared to the model group, weight, bloodglucose,HOMA-IR decreased and insulin rises (P<0.05). No difference amongthe three groups of C57BL/6J mice in glucose., and no difference between theC57intervention group and C57control group in body weight, insulin andHOMA-IR (P>0.05). C57intervention group had lower body weight, insulinand HOMA-IR than C57model group,(P<0.05).2.Steatosis and inflammation, hepatocyte ballooning were not seen incontrol group, while the2model groups was diffuse macrovesicular or microvesicular steatosis, the bullous based mixed steatosis, theliver cells of fatty degeneration were more than2/3. Lobularinflammation and hepatocyte ballooning were found in the2model groups.There was significant difference between control and model groups(P＜0.01). The NASH conditions of the2intervention groups were better thanthe model groups（P<0.01）. Every group had not severe hepatic fibrosis. The2intervention groups only had tiny hepatic fibrosis, compared with the2modelgroups(p<0.01). There were significant increases of intracellular TGaccumulation in live in C57model group，intervention group and DB modelgroup， intervention group，compared with control group（P<0.01）.And the2intervention groups ‘s intracellular TG accumulation were lower than themodel groups，（P<0.05）.3.Each group liver AC3mRNA expression comparison: db/db mice, theintervention group’s AC3mRNA expression level was significantly increasedcompared with model group,(P<0.05). C57model group’s and interventiongroup’s AC3mRNA expression was significantly reduced compared withcontrol group,(P<0.05); the C57intervention group AC3mRNA expression wassignificantly increased compared with C57model group (P<0.05).4.There was a significant association between liver cytosolicTG accumulation and body weight（r＝0.898，P <0.001）; between livercytosolic TG accumulation and HOMA-IR（r＝0.836，P <0.001）. livercytosolic TG accumulation and expression of AC3-mRMA （r＝－0.818，P<0.001）Conclusion:1、 liraglutide can improve glucose, lipid metabolism and insulin resistance, NASH mice’s liver pathologic changes while attenuating weightgain, liraglutide might play an effective role in the treatment of Obesity andnonalcoholic fatty liver disease.2.liraglutide can reversed Obesity and nonalcoholic fatty liverdisease,insulin resistance by increasing the expression of AC3.