LiGHRKO Male Mice Non-alcoholic Fatty Liver Disease Model Establishment And Phenotype Analysis

Non-alcoholic fatty liver disease(NAFLD)is one of the types of fatty liver which occurs when fat is deposited in the liver due to causes other than excessive alcohol use includes a spectrum of histopathological findings.Research showed that low circulating growth hormone(GH)level or hepatic GH signaling impairment are associated with NAFLD;Insulin like growth hormone factor 1(IGF-1)is manly synthesized in liver with the mediation of GH;Clinical observation found out that low levels of IGF-1 are correlated with hepatic lipid accumulation,and IGF-1 levels are negatively related to the lipid overload in liver.In this study,hepatic deletion of growth hormone receptor in mice(LiGHRKO)was used to analyse the relationship between GH/IGF-1 axis and NAFLD,and compare this model with high fat diet induced NAFLD animal model.It is an excellent animal model for better understanding the pathological of NAFLD and the impacts of IGF-1 in the development of NAFLD.Glucose tolerance test and insulin tolerance test were conducted and mice were killed,the tissue samples and serum were collected for further pathology and serological analysis.The results are as follows:1.With double verification of DNA and RNA levels,GHR was successfully knockout in the liver of LiGHRKO male mice.The GH level was 4 times higher in LiGHRKO male mice than control mice,and the IGF-1 level dropped 90%.2.The body weight of LiGHRKO male mice than control mice and HF mice.The liver were bigger in LiGHRKO male mice and the liver index(liver weight/body weight)were significantly higher in LiGHRKO male mice and HF mice.The weight of other major organs was almost same in these three group mice.Serum levels of VLDL,T-CHO,transaminase(AST/ALT)and TNF-α were significantly elevated in LiGHRKO male mice and HF mice(P<0.05).LiGHRKO male mice and HF mice showed impaired glucose tolerance and insulin tolerance,their glucose metabolism was abnormal.3.Pthology study(H&E staining)showed swollen hepatocyte in LiGHRKO male mice and HF mice.The The Oil red O staining revealed bigger droplets in LiGHRKO male mice and HF mice than in control mice.ROS level was increased in LiGHRKO mice and HF mice,indicating mitochondrial dysfunction.In summary,LiGHRKO male mice exhibited typical phenotypes of non-alcoholic fatty liver such as imbalance of glucose and lipid metabolism,insulin resistance,hepatic fat accumulation,and mitochondrial dysfunction.The modeling method achieves the effect of high-fat feeding and modeling.