Effects Of Acute Liver Injury In Mice On Adipose Tissue And Its Mechanism

Objective:CCl₄ was used to prepare acute liver injury model,the morphology of inguinal white adipose tissue,epididymal white adipose tissue and intercalar brown adipose tissue were observed at the end of 2 and 4 weeks,and the expression of uncoupling protein 1（UCP1）was detected,to explore the effect of acute liver injury on different adipose tissue,and to briefly explore the possible mechanism of this process.Methods:Eighteen 8-week-old C57BL/6 male mice were randomly divided into three groups（n=6）:control group（Ctrl）,CCl₄ 2 weeks group（CCl₄ 2-week）and CCl₄ 4 weeks group（CCl₄ 4-week）.In the CCl₄ group,25%CCl₄ was injected intraperitoneally（ip）at a dose of 0.1 ml/10 g every 3 days,twice in total;in the control group,olive oil of the same dose was given.At the end of 2 weeks and 4 weeks respectively,blood was collected from the hearts of mice in each group after anesthesia with 1%Pentobarbital Sodium.The liver,inguinal white adipose tissue,epididymal white adipose tissue and intercalar brown adipose tissue were obtained.He staining was used to observe the morphological changes of liver,inguinal white adipose tissue,epididymal white adipose tissue and intercalar brown adipose tissue;immunohistochemistry staining and real-time quantitative PCR were used to detect the expression of UCP1 in inguinal white adipose tissue,epididymal white adipose tissue and intercalar brown adipose tissue;enzyme-linked immunosorbent assay（ELISA）was used to detect the content of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）and tumor necrosis factor-α（TNF-α）in serum.Pearson method was used to test the relationship between UCP1mRNA levels and TNF-αcontent.Results:1.In the CCl₄ 2-week group,the hepatocytes were loose in cytoplasm,disorganized in arrangement,dilated in hepatic sinuses,small pieces of necrosis and a large number of inflammatory cell infiltration were observed,and the contents of ALT and AST in serum were significantly increased.In the CCl₄ 4-week group,the structure of hepatocytes tended to be normal and arranged orderly,with punctate necrosis and a small amount of inflammatory cell infiltration,and the content of ALT and AST in serum decreased.2.In the CCl₄ 2-week group,the lipid droplets of inguinal white adipocytes,epididymal white adipocytes and intercalar brown adipocytes increased,the expression of UCP1 protein in adipose tissue decreased,and the level of UCP1 mRNA decreased;in the CCl₄ 4-week group,the lipid droplets of inguinal white adipocytes,epididymal white adipocytes and intercalar brown adipocytes decreased,and the level of UCP1 mRNA in adipose tissue increased.3.The content of TNF-αin the serum of CCl₄ 2-week group increased,while that of CCl₄ 4-week group decreased.4.The levels of UCP1 mRNA in inguinal white adipose tissue,epididymal white adipose tissue and intercalar brown adipose tissue of mice in CCl₄ 2-week and CCl₄4-week groups were negatively correlated with serum TNF-α.Conclusion:After acute liver injury in mice caused a decline in liver function,the lipid droplets of white adipocytes and brown adipocytes increased and the expression of UCP1 in adipose tissue decreased,the energy consumption decreased,and the body heat production decreased,which affected the metabolic homeostasis and energy balance.However,after the recovery of liver function in mice,the above changes were reversed,and the mechanism may be related to the change of TNF-αcontent caused by liver injury.