Development of a short-term mouse model of early MASLD for non-invasive pathophysiological tracking via urinary...

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are common chronic liver disorders linked to hepatocellular carcinoma. However, the lack of time-efficient preclinical models, coupled with the shortage of integrated and longitudinal non-invasive monitoring strategies, has restricted mechanistic investigations and therapeutic development.

This study aimed to establish a short-term modified Western diet (mWD)-induced MASLD model in middle-aged mice and to evaluate the feasibility of integrating urinary metabolomics and micro-computed tomography (Micro-CT) for non-invasive tracking of metabolic and imaging changes associated with early-stage MASLD.

Ten-month-old mice were fed a high-fat, high-fructose mWD for 90 days, with systematic assessments of food and water intake, body weight, body composition, and urinary metabolite profiles conducted throughout the intervention. At the endpoint, oral glucose tolerance tests (OGTT) and micro-CT scans were performed to characterize key metabolic and imaging phenotypes in this dietary model.

mWD feeding was associated with significant adiposity gain, glucose metabolism impairment, and systemic metabolic reprogramming in mice. Untargeted urinary metabolomics further revealed progressive perturbations in lipid and amino acid metabolic pathways, as well as candidate biomarkers associated with diet-induced metabolic alterations.

Collectively, this work provides initial proof-of-concept for the feasibility of integrating urinary metabolomics with micro-CT for non-invasive monitoring of an early MASLD-like phenotype, and a basis for future studies incorporating histopathological and cardiometabolic confirmation.