Post-Bariatric Surgery Changes in Quinolinic and Xanthurenic Acid Concentrations Are Associated with Glucose Homeostasis

PLoS One. 2016 Jun 21;11(6):e0158051. doi: 10.1371/journal.pone.0158051. eCollection 2016.

Abstract

Background: An increase of plasma kynurenine concentrations, potentially bioactive metabolites of tryptophan, was found in subjects with obesity, resulting from low-grade inflammation of the white adipose tissue. Bariatric surgery decreases low-grade inflammation associated with obesity and improves glucose control.

Objective: Our goal was to determine the concentrations of all kynurenine metabolites after bariatric surgery and whether they were correlated with glucose control improvement.

Design: Kynurenine metabolite concentrations, analysed by liquid or gas chromatography coupled with tandem mass spectrometry, circulating inflammatory markers, metabolic traits, and BMI were measured before and one year after bariatric surgery in 44 normoglycemic and 47 diabetic women with obesity. Associations between changes in kynurenine metabolites concentrations and in glucose control and metabolic traits were analysed between baseline and twelve months after surgery.

Results: Tryptophan and kynurenine metabolite concentrations were significantly decreased one year after bariatric surgery and were correlated with the decrease of the usCRP in both groups. Among all the kynurenine metabolites evaluated, only quinolinic acid and xanthurenic acid were significantly associated with glucose control improvement. The one year delta of quinolinic acid concentrations was negatively associated with the delta of fasting glucose (p = 0.019) and HbA1c (p = 0.014), whereas the delta of xanthurenic acid was positively associated with the delta of insulin sensitivity index (p = 0.0018).

Conclusion: Bariatric surgery has induced a global down-regulation of kynurenine metabolites, associated with weight loss. Our results suggest that, since kynurenine monoxygenase diverts the kynurenine pathway toward the synthesis of xanthurenic acid, its inhibition may also contribute to glucose homeostasis.

MeSH terms

  • Adult
  • Bariatric Surgery*
  • C-Reactive Protein / metabolism
  • Diabetes Mellitus / blood
  • Female
  • Glucose / metabolism*
  • Homeostasis*
  • Humans
  • Kynurenine / blood
  • Metabolome
  • Quinolinic Acid / blood*
  • Serotonin / blood
  • Tryptophan / blood
  • Xanthurenates / blood*

Substances

  • Xanthurenates
  • Serotonin
  • Kynurenine
  • xanthurenic acid
  • Tryptophan
  • C-Reactive Protein
  • Quinolinic Acid
  • Glucose

Grants and funding

This work was supported by grants from the CNRS (http://www.cnrs.fr/); the “Société Francophone du Diabète”(http://www.sfdiabete.org/), “European Genomic Institute for Diabetes” (E.G.I.D., ANR-10-LABX-46; http://www.egid.fr) and European Commission (http://ec.europa.eu). MF is supported by a doctoral grant from the “Conseil Régional du Nord-Pas de Calais” (http://www.nordpasdecalais.fr) and from the “CHRU de Lille” (http://www.chru-lille.fr/). GJG is supported by the Australian Research Council (ARCF20100397)(http://www.arc.gov.au/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.