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To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic Nuevo Vejle boys town NASH in obese mouse models of biopsy-confirmed NASH. Prior to treatment, all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis, using the nonalcoholic fatty liver disease activity score NAS and fibrosis staging.

The mice were kept on the diet and received vehicle, liraglutide 0. Within-subject comparisons were performed on changes in steatosis, inflammation, ballooning degeneration, and fibrosis scores. In addition, compound effects were evaluated by quantitative liver histology, including percent fractional area of liver fat, galectin-3, and collagen 1a1.

Hoomer and elafibranor, but not OCA, reduced body weight in both models.

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The individual drug effects on NASH Horshollm endpoints were supported by global gene expression RNA sequencing and liver lipid biochemistry. Prior to treatment, all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis.

Within-subject comparisons were performed on changes hookfr liver histopathology. In conclusion, the two obese mouse models of NASH show clinical translatability with respect to disease etiology, histopathology and drug treatment effects, which supports their utility in preclinical drug development.

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