Journal of Clinical Hepatology
This article aims to explore whether the MASH mouse model induced by high-fat, high-sugar, high-cholesterol diet combined with intraperitoneal injection of carbon tetrachloride (CCl₄) can effectively simulate the bile acid spectrum changes in clinical MASH patients and assess its feasibility for drug intervention research. The study found that the model group mice showed typical MASH features, including liver fatty degeneration, inflammatory infiltration, fibrosis progression (F2–F4 stage), and elevated levels of ALT, AST, and TG. The detection using ultra-performance liquid chromatography-tandem mass spectrometry showed that the total bile acids in the liver tissue of the model group increased, and toxic bile acids such as CA, GCA, CDCA, GCDCA were significantly upregulated, while protective bile acids such as UDCA, TUDCA decreased. This trend is highly similar to the bile acid disorder in clinical MASH patients. The innovation lies in the first systematic depiction of the dynamic bile acid spectrum evolution under the complex modeling method and the verification of its similarity to the metabolic phenotype of human diseases, providing reliable animal model support for the subsequent development of drugs targeting the bile acid pathway.
This study systematically observed the liver pathological changes and bile acid spectrum evolution during the disease progression by constructing a MASH mouse model induced by high-fat, high-sugar, high-cholesterol diet combined with carbon tetrachloride (WD+CCl₄). The study found that with the progression of fibrosis, fatty degeneration showed progressive reduction, which conforms to the pathological characteristics of clinical MAFLD developing into fibrosis, indicating that the model has good clinical simulation. At the same time, the total bile acid level in the liver of the model group mice significantly increased, and various bile acid components such as CA, CDCA, and their conjugates changed significantly at different time points, and the trend of change is similar to the bile acid spectrum of human MASH patients. This indicates that the WD+CCl₄-induced MASH model can not only stably reproduce the key pathological features of the disease but also accurately reflect the dynamic process of bile acid metabolism disorder. Therefore, the model provides a reliable experimental platform for exploring the pathogenesis of MASH and evaluating the intervention effect of drugs targeting bile acid metabolism, and has important translational medical value.
Objective: To compare the hepatic bile acid profile between a mouse model of metabolic-associated steatohepatitis (MASH) induced by a…
