Western Diet Combined With Chemical Induction: A Strategy for Rapid Development of MASLD Pathology in Mice

The molecular mechanisms underlying the development of metabolic‐dysfunction‐associated steatotic liver disease (MASLD) are essential for developing appropriate treatments. The purpose of this study was to establish an MASLD model in mice with rapid and consistent progression. Male C57BL/6J mice were randomized into the normal diet control group, ND + CCl 4 group, Western diet (WD) group, and WD + CCl 4 group. During 16 weeks of modeling, body weight, blood glucose, liver/kidney echo signal ratio, serum biochemical indicators, hepatic histopathology, inflammatory cytokines, oxidative stress levels, and protein expressions related to lipid synthesis and fibrosis were detected. The results showed that compared with the ND + CCl 4 group and WD group, the WD + CCl 4 group exhibited more significant metabolic disorders, including elevated blood glucose, serum transaminases, and lipid profiles. Meanwhile, hepatic steatosis, inflammatory cell infiltration, hepatocyte ballooning, and collagen deposition were markedly aggravated, accompanied by upregulated inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α), enhanced oxidative stress, and increased protein expression of fatty acid synthase and alpha‐smooth muscle actin. Collectively, the WD + CCl 4 group represented more severe and significant features of metabolic dysfunction‐associated steatohepatitis (MASH), such as steatosis, inflammatory cell infiltration, and even fibrosis. Therefore, our study demonstrated that CCl 4 accelerates liver fibrosis on the basis of WD feeding, suggesting that WD combined with CCl 4 is an ideal method to establish an MASLD model.