Hepatoprotective effects of late-stage clinical drug candidates and dietary intervention in the non-obese CDAA-HFD mouse model of advanced MASH with progressive fibrosis

We applied RNA sequencing (RNA-seq) to study the gene expression profile in the liver of mice fed the CDAA-HFD for 3 weeks (n=9), 6 weeks (n=10), 12 weeks (n=8) and 20 weeks (n=8) and lean chow controls (n=8). At all timepoints, CDAA-HFD mice displayed a widespread increase in the expression of MASH candidate genes related to inflammation, hepatocellular injury and ECM organization as compared to chow-fed controls. Gene expression was further studied in response to chow reversal (n=9), semaglutide (n=9) and lanifibranor (n=10) as compared to Vehicle (n=10). Chow reversal and lanifibranor, induced wide-spread transcriptional changes in MASH candidate genes while semaglutide showed only discrete effects on candidate genes. RNA-seq of RNA isolated from mice fed CDAA-HFD for 3-20 weeks (n=8-10/group) and healthy controls (n=8), and CDAA-HFD fed mice treated with Vehicle, Semaglutide, Lanifibranor and Chow-reversal (n=9-10/group).