Purpose: The purpose of this study is to elucidate the differences in hepatic metabolites between two animal models of nonalcoholic fatty liver disease (NAFLD), namely methionine and choline-deficient (MCD) diet and high-fat diet (HFD), and to investigate the association with fatty acids.
Materials and methods: This experiment was designed with three groups exposed to methionine and choline-deficient diet, high-fat diet, and normal diet, respectively. The profiles of fat in each model were acquired using 9.4T MRS and the obtained data were quantified as signal values relative to water using LC model software. Subsequently, NMR sampling was performed on extracted liver tissue using a Bruker Avance III 700MHz NMR spectrometer. The obtained NMR metabolite data were quantified using Chenomx software, and valid metabolites were analyzed using SIMCA statistical analysis. The effective metabolites obtained from SIMCA and the quantified fat values from LC model were analyzed using SPSS for mean comparison and correlation analysis.
Results: Metabolites contributing to the separation of three groups were identified using OPLS-DA. Betaine and Glycerol were among the significant metabolites. Correlation analysis revealed a negative association between betaine and fat content, and a positive association between cadaverine, caprylate, niacinamide, and unsaturated fatty acid at 2.8ppm. MCD had the highest levels of these metabolites.
Conclusion and discussion: Differences in hepatic metabolites were found between MCD and HFD animal models, with higher levels of unsaturated fatty acids in MCD. These findings can serve as a basis for experimental and therapeutic approaches in fatty liver disease. The negative correlation between betaine and fat content suggests that betaine may be a metabolite that reduces fat accumulation.
Key Words: Fatty liver disease, methionine and choline deficient diet, high fat diet, 9.4T MRI, liver damage