【Animal Modeling】-Effect and mechanism of acute liver injury in mice on brown adipose tissue function

  Objective To investigate the effects of carbon tetrachloride (CC14 ) on brown adipose tissue in mice with acute liver injury at different time points and the related mechanisms.

  Methods Eighteen 8-week-old C57BL/6 male mice were randomly divided into control group, CC14 2-week group, and CC14 4-week group, with 6 mice in each group. The CC14 group was injected with CC14 twice, and the control group was given the same dose of olive oil. Brown adipose tissue was weighed, the pathological changes of liver and brown adipose tissue were observed by HE staining, the expression of brown adipose tissue uncoupling protein 1 (UCP1) was detected by immunohistochemistry and real-time quantitative PCR, and the enzyme-linked immunosorbent assay (ELISA) method was used to detect the expression of brown adipose tissue. The contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and tumor necrosis factor-α (TNF-α) in serum were tested by Pearson method to test the relationship between the level of UCP1 mRNA and the content of TNF-α.

  Results Compared with the control group, the CC14 2-week group had increased serum ALT and AST levels (P<0.01), decreased brown adipose tissue weight (P<0.05), decreased UCP1 protein expression (P<0.05), and decreased UCP1 mRNA expression (P<0.05). Compared with the CC14 2-week group, the serum ALT and AST contents of the CC14 4-week group decreased (P<0.05), and the brown adipose tissue weight increased (P<0.05). 0.05), the expression of UCP1 mRNA increased (P<0.01), and the content of TNF-α in serum decreased (P<0.001). The levels of UCP1 mRNA in CC14 2-week group and CC14 4-week group were significantly negatively correlated with TNF-α content (r =-0.950, P<0.01, r=-0.859, P<0.05).

  Conclusion Acute liver injury can lead to the decline of brown adipose tissue function and the reduction of body heat production, thereby affecting metabolic homeostasis. The mechanism may be related to the increase of TNF-α content.