RNA-seq of liver from AHR-deficient MAFLD rats
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common chronic liver disease driven by lipid metabolism disorders. In this study, we established an MAFLD model by generating aryl hydrocarbon receptor (AHR) knockout (AHR-/-) and wild-type (WT) rats and feeding them a high-fat, high-fructose, high-cholesterol diet (HFHFrHCD) for 10 weeks. Comprehensive phenotypic analysis showed that under conditions of nutrient excess, AHR deficiency exacerbated liver injury, hepatic triglyceride and cholesterol accumulation, and insulin resistance. To elucidate the underlying molecular mechanisms, we performed RNA sequencing (RNA-seq) on liver tissues from AHR-/- and WT rats. Transcriptomic analysis revealed a significant downregulation of the bile acid biosynthesis pathway, particularly a decrease in the expression of the rate-limiting enzyme CYP7A1 in the classical bile acid synthesis pathway.