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An Experimental DUAL Model of Advanced Liver Damage.

Raquel Benedé-Ubieto1,2, Olga Estévez-Vázquez1,2, Feifei Guo2

  • 1Department of Physiology, Genetics and MicrobiologyFaculty of BiologyComplutense University MadridMadridSpain.

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Summary

A new DUAL mouse model combining alcohol and Western diet shows obesity, liver damage, and fibrosis. This model mimics human advanced steatohepatitis, offering a tool for developing new therapies.

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Area of Science:

  • Hepatology and Metabolic Diseases
  • Preclinical Disease Modeling

Background:

  • Metabolic and alcohol-associated liver diseases often co-exist in patients.
  • A combined preclinical model is needed to study this dual pathology.

Purpose of the Study:

  • To develop and characterize a preclinical DUAL (alcohol-associated liver disease + metabolic-associated fatty liver disease) mouse model.
  • To investigate the histological, metabolic, and transcriptomic changes in this model.

Main Methods:

  • C57BL/6 mice were fed alcohol and a Western diet for 10, 23, and 52 weeks.
  • Metabolic parameters, liver histology, and bulk RNA-sequencing were analyzed.
  • White adipose tissue was also examined for inflammation and fibrosis.

Main Results:

  • DUAL mice exhibited increased BMI, adipocyte hypertrophy, hypercholesterolemia, and hyperglycemia.
  • Significant liver damage included elevated liver enzymes, hepatomegaly, steatosis, inflammation, and advanced fibrosis, progressing to cirrhosis.
  • Transcriptomic analysis revealed pathways similar to human steatohepatitis.

Conclusions:

  • The DUAL model recapitulates key features of human advanced steatohepatitis, including obesity, metabolic dysfunction, and liver fibrosis.
  • This model demonstrates inflammation and fibrosis in white adipose tissue.
  • The DUAL model serves as a valuable preclinical tool for therapeutic target development.