GSE161147
Transcriptomic changes assoicated with hepatic AHR or ARNT loss in female mice challenged with high-fat diet
The aryl hydrocarbon receptor (AHR) is an important hepatic transcription factor that appears to have a role in regulating endogenous liver metabolism. Canonical AHR-mediated regulation of transcription requires AHR binding to its DNA-binding partner, the AHR nuclear translocator (ARNT). We previously demonstrated that the AHR can regulate transcription independent of ARNT via “non-canonical” interactions with Kruppel-like factor 6, and that hepatic AHR loss can protect against high-fat diet (HFD) challenge. In this study, we examined the effects of hepatic AHR or ARNT loss in HFD-fed mice to determine whether AHR regulation of liver metabolism might partially occur independent of ARNT. The data show that similar to AHR loss, ARNT loss reduces HFD-driven hepatic lipid deposition, but does not recapitulate the diminished weight gain and adiposity observed in AHR KO animals. Utilizing transcriptomic sequencing analyses, we uncovered specific gene pathways that likely account for these phenotypic differences/similarities associated with AHR or ARNT loss. Together, these data highlight the physiological significance of ARNT-independent AHR activity, and identify discrete aspects of liver metabolism likely regulated via canonical AHR action. Overall design: Next Generation Sequencing of adult female mice (6 months old, n=3 per genotype). All mice were maintained on a high-fat diet for 13 weeks. Genotypes: Ahr Flox, AHR KO, ARNT Flox, ARNT KO