Kynurenic acid, an aryl hydrocarbon receptor ligand, is elevated in serum of Zucker fatty rats

Obesity is an increasingly urgent global problem and the molecular mechanisms of obesity are not fully understood. Dysregulation of the tryptophan (Trp) – kynurenine (Kyn) metabolic pathway (TKP) have been suggested as a mechanism of obesity and described in obese humans and in animal models of obesity. However, to the best of our knowledge, TKP metabolism has not been studied in leptin-receptor-deficient Zucker fatty rats (ZFR) (fa/fa), the best-known and most widely used rat model of obesity. We were interested to determine if there are any deviations of TKP in ZFR. Concentrations of major TKP metabolites were evaluated (HPLC- MS method) in serum of ZFR (fa/fa) and age-matched lean rats (FA/-). Concentrations of kynurenic acid (KYNA) were 50% higher in ZFR than in lean rats (p<0.004, Mann-Whitney two-tailed test). Anthranilic acid (AA) concentrations, while elevated by 33%, did not reach statistical significance (p<0.04, one-tailed test). Elevated KYNA serum concentrations might contribute to development of obesity via KYNA-induced activation of aryl hydrocarbon receptor. Present results warrant further studies of KYNA and AA in ZFR and other animal models of obesity.