biostudies-literatureUnknown29(2)Morgan EWDiet-phytochemical derived activation, host and microbial tryptophan metabolism represent the dominant route to endogenously mediated stimulation of physiological Ah receptor (AHR) activity. Whether host tryptophan metabolism provides a phytochemical independent circadian AHR tone has not been established. Using mice maintained on a nocturnally restricted feeding schedule with a nutritionally defined diet, we utilized quantitative gene/protein expression analyses in conjunction with targeted metabolomics to examine the temporal relationship between host tryptophan metabolism and circadian AHR activity. Time-resolved, targeted LCMS metabolomic, gene, and protein expression analyses reveal circadian cycling of hepatic tryptophan metabolizing enzymes (TDO2, TAT, GOT1, GOT2, KAT1, KAT2, and ILiScience114680https://www.ebi.ac.uk/biostudies/studies/S-EPMC12919285biostudies-literatureCircadian tryptophan metabolism contributes to systemic aryl hydrocarbon receptor activity.PMC12919285Patterson ADPerdew GHMorgan EWMurray IACoslo DMfalseCircadian tryptophan metabolism contributes to systemic aryl hydrocarbon receptor activity.Diet-phytochemical derived activation, host and microbial tryptophan metabolism represent the dominant route to endogenously mediated stimulation of physiological Ah receptor (AHR) activity. Whether host tryptophan metabolism provides a phytochemical independent circadian AHR tone has not been established. Using mice maintained on a nocturnally restricted feeding schedule with a nutritionally defined diet, we utilized quantitative gene/protein expression analyses in conjunction with targeted metabolomics to examine the temporal relationship between host tryptophan metabolism and circadian AHR activity. Time-resolved, targeted LCMS metabolomic, gene, and protein expression analyses reveal circadian cycling of hepatic tryptophan metabolizing enzymes (TDO2, TAT, GOT1, GOT2, KAT1, KAT2, and IL2026-01-01T00:00:00Z2026 Feb2026-07-16T17:55:36.679Z2026-07-09T11:10:14.971ZS-EPMC129192854172718210.1016/j.isci.2026.114680