Abstract： Objective:To observe the expression of farnesoid X receptor (FXR) and metallothionein 1 (MT1) in the liver of mice with fatty liver, the regulation of MT1 by FXR and agonist obecocholic acid (OCA) in mouse liver.Methods:Sixteen 6-week-old male C57BL/6 mice [with a body weight of (20±1.5) g] were treated with 45% FAT high-fat diet (HFD) and 10% FAT control feed (CON) for 12 weeks to induce non-alcoholic fatty liver disease (NAFLD) animal models. They were divided into HFD group and CON group ( n=8) , and qPCR was used to detect FXR at mRNA level changes in MT1 expression of the liver. C57BL/6 mice were treated with the artificially synthesized FXR agonist OCA for 3 days and divided into OCA group and CON group ( n=8) . The expression changes of MT1 were detected at the mRNA and protein levels using qPCR and immunoblotting methods, respectively. Different concentrations of OCA (0, 0.1, 0.5, 1, 2, 5 μmol/L groups) were used to treat human liver cancer cell line HepG2 cells for 24 hours, or FXR adenovirus (divided into Ad FXR group and Ad GFP group) was overexpressed for 24 hours. Application of qPCR to detect changes in MT1A expression of cells at mRNA level. A mouse MT1 promoter luciferase reporter gene was constructed and transfected into HEK293T cells. After treatment with OCA or dimethyl sulfoxide (DMSO) for 24 hours, the cells were lysed and luciferase activity was detected to explore the regulatory effect of OCA on MT1 promoter activity. Results:(1) Compared to the CON group diet, HFD diet can induce obesity in mice, increase blood lipid levels, and lead to significant lipid transformation in the liver. The liver lipid content is significantly increased, and the expression of FXR and MT1 in the liver is reduced (both P<0.05) . (2) OCA treatment significantly upregulated the mRNA and protein levels of MT1 in mouse liver (both P<0.05) . (3) When treated with different concentrations of OCA in cultured HepG2 cells, it was found that compared with the control group, OCA 0.5 μmol/L treatment can increase the mRNA expression level of MT1A in HepG2 cells ( P<0.05) . (4) Adenovirus mediated overexpression of FXR can upregulate the expression level of MT1A mRNA in HepG2 cells ( P<0.05) . (5) The luciferase reporter gene method further confirms that OCA treatment can enhance the promoter activity of MT1 in mice ( P<0.05) , which is 1.98 times higher than the control group. Conclusion:The mouse MT1 gene can be regulated at the transcriptional level by the FXR agonist OCA, OCA may play a role in regulating the process of NAFLD by inducing the expression of MT1 in mice.