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. 2016;3(4):761-763.
Epub 2016 Aug 29.

Kynurenic Acid, an Aryl Hydrocarbon Receptor Ligand, Is Elevated in Serum of Zucker Fatty Rats

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Free PMC article

Kynurenic Acid, an Aryl Hydrocarbon Receptor Ligand, Is Elevated in Serum of Zucker Fatty Rats

G Oxenkrug et al. Integr Mol Med. .
Free PMC article

Abstract

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.

Keywords: aryl hydrocarbon receptor; kynurenic acid; metabolic syndrome; obesity; zucker fatty rats.

Figures

Figure 1
Figure 1
Three major phases of Tryptophan – Kynurenine metabolic pathway. Abbreviations: Trp: tryptophan; Kyn: kynurenine; KYNA: kynurenic acid; 3HK: 3-hydroxykynurenine; AA: anthranilic acid; 3HAA: 3-hydroxyanthranilic acid; XA: xanthurenic acid (3-hydroxyKYNA); NAD+: nicotinamid adenine dinucleotide; KMO: kynurenine 3-monooxygenase; Kynu: kynureninase; KAT: kynurenine aminotransferase 2

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References

    1. Oxenkrug GF. Metabolic syndrome, age-associated neuroendocrine disorders, and dysregulation of tryptophan-kynurenine metabolism. Ann N Y Acad Sci. 2010;1199:1–14. - PubMed
    1. Oxenkrug G. 3-hydroxykynureninc acid and type 2 diabetes: implications for aging, obesity, depression, Parkinson’s disease and schizophrenia. In: Engin A, Engin AB, editors. Tryptophan Metabolism: Implications for Biological Processes, Health and Diseases, Molecular and Integrative Toxicology. 2015. pp. 173–195.
    1. Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ. Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci. 2012;13:465–477. - PMC - PubMed
    1. Favennec M, Hennart B, Caiazzo R, Leloire A, Yengo L, et al. The Kynurenine Pathway is Activated in Human Obesity and Shifted Toward Kynurenine Monooxygenase Activation. Obesity. 2015;23:2066–2074. - PubMed
    1. Guillemin GJ, Smith DG, Kerr SJ, Smythe GA, Kapoor V, et al. Characterisation of kynurenine pathway metabolism in human astrocytes and implications in neuropathogenesis. Redox Rep. 2000;5:108–111. - PubMed

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