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<p>For decades, investigators have pursued the development of a comprehensive rodent model that fully recapitulates the pathophysiology of metabolic dysfunction-associated steatotic liver disease (MASLD) and mimics human disease. Dietary models are generally considered the most reliable for recapitulating human disease; however, no dietary rodent model has yet been reported with high similarity to human MASLD, limiting the study of pathophysiology and treatment strategies for advanced fibrosis and portal hypertension. Here we conducted a multistep, sequential refinement of our MASLD model in rats until we achieved a comprehensive model that reproduced the clinical features of metabolic syndrome, steatohepatitis, advanced fibrosis and portal hypertension with a transcriptomic profile resembling human MASLD. The final model consisted of a 20-week high-fat diet with high concentrations of cholesterol (2%) and a glucose–fructose beverage; in this model, the addition of cholic acid at low concentrations (0.1%) substantially increased the percentage of rats achieving fibrosis stage ≥F2 at the endpoint. Owing to its short duration, simplicity, versatility and strong translational relevance to human MASLD, the proposed model could potentially serve a wide range of investigators working in the field of metabolism and liver disease, facilitating meaningful advances in mechanistic studies and the development of new therapeutics.</p>

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Development and characterization of dietary models of MASLD with portal hypertension and liver fibrosis in rats

  • 期刊论文

  • 发表日期：

    2026年4月3日

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  • María Martínez-Gómez,
  • Aurora Barberá,
  • Imma Raurell,
  • M. Serra Cusidó,
  • Sophia C. Parks,
  • M. Teresa Salcedo,
  • Salvador Augustin,
  • Meritxell Ventura-Cots,
  • Joan Genescà,
  • María Martell,
  • Juan M. Pericàs

摘要

For decades, investigators have pursued the development of a comprehensive rodent model that fully recapitulates the pathophysiology of metabolic dysfunction-associated steatotic liver disease (MASLD) and mimics human disease. Dietary models are generally considered the most reliable for recapitulating human disease; however, no dietary rodent model has yet been reported with high similarity to human MASLD, limiting the study of pathophysiology and treatment strategies for advanced fibrosis and portal hypertension. Here we conducted a multistep, sequential refinement of our MASLD model in rats until we achieved a comprehensive model that reproduced the clinical features of metabolic syndrome, steatohepatitis, advanced fibrosis and portal hypertension with a transcriptomic profile resembling human MASLD. The final model consisted of a 20-week high-fat diet with high concentrations of cholesterol (2%) and a glucose–fructose beverage; in this model, the addition of cholic acid at low concentrations (0.1%) substantially increased the percentage of rats achieving fibrosis stage ≥F2 at the endpoint. Owing to its short duration, simplicity, versatility and strong translational relevance to human MASLD, the proposed model could potentially serve a wide range of investigators working in the field of metabolism and liver disease, facilitating meaningful advances in mechanistic studies and the development of new therapeutics.