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


METHODS
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).


CONCLUSIONS
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.
Univ. Lille, UMR 8199 - EGID, F-59000 Lille, France.|CNRS, UMR 8199, F-59000 Lille, France.|Institut Pasteur de Lille, F-59000 Lille, France.
Marie
M
Favennec
Univ. Lille, EA 4483 - IMPECS - IMPact de l'Environnement Chimique sur la Santé humaine, F-59000 Lille, France.|CHU Lille, Service de Toxicologie-Génopathies, F-59000 Lille, France.
Benjamin
B
Hennart
Univ. Lille, UMR 8199 - EGID, F-59000 Lille, France.|CNRS, UMR 8199, F-59000 Lille, France.|Institut Pasteur de Lille, F-59000 Lille, France.
Marie
M
Verbanck
Univ. Lille, U1190 - EGID, F-59000 Lille, France.|Inserm, U1190, F-59000 Lille, France.|CHU Lille, Chirurgie générale et endocrinienne, F-59000 Lille, France.
Marie
M
Pigeyre
Univ. Lille, U1190 - EGID, F-59000 Lille, France.|Inserm, U1190, F-59000 Lille, France.|CHU Lille, Chirurgie générale et endocrinienne, F-59000 Lille, France.
Robert
R
Caiazzo
Univ. Lille, U1190 - EGID, F-59000 Lille, France.|Inserm, U1190, F-59000 Lille, France.|CHU Lille, Chirurgie générale et endocrinienne, F-59000 Lille, France.
Violeta
V
Raverdy
Univ. Lille, U1190 - EGID, F-59000 Lille, France.|Inserm, U1190, F-59000 Lille, France.|CHU Lille, Chirurgie générale et endocrinienne, F-59000 Lille, France.
Hélène
H
Verkindt
Univ. Lille, UMR 8199 - EGID, F-59000 Lille, France.|CNRS, UMR 8199, F-59000 Lille, France.|Institut Pasteur de Lille, F-59000 Lille, France.
Audrey
A
Leloire
Neuroinflammation group, Macquarie University, Sydney, NSW, 2109 Australia.
Gilles J
GJ
Guillemin
Univ. Lille, UMR 8199 - EGID, F-59000 Lille, France.|CNRS, UMR 8199, F-59000 Lille, France.|Institut Pasteur de Lille, F-59000 Lille, France.
Loïc
L
Yengo
Univ. Lille, EA 4483 - IMPECS - IMPact de l'Environnement Chimique sur la Santé humaine, F-59000 Lille, France.|CHU Lille, Service de Toxicologie-Génopathies, F-59000 Lille, France.
Delphine
D
Allorge
Univ. Lille, UMR 8199 - EGID, F-59000 Lille, France.|CNRS, UMR 8199, F-59000 Lille, France.|Institut Pasteur de Lille, F-59000 Lille, France.|Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, United Kingdom.
Philippe
P
Froguel
Univ. Lille, U1190 - EGID, F-59000 Lille, France.|Inserm, U1190, F-59000 Lille, France.|CHU Lille, Chirurgie générale et endocrinienne, F-59000 Lille, France.
François
F
Pattou
Univ. Lille, UMR 8199 - EGID, F-59000 Lille, France.|CNRS, UMR 8199, F-59000 Lille, France.|Institut Pasteur de Lille, F-59000 Lille, France.
Odile
http://orcid.org/0000-0001-8805-9450
O
Poulain-Godefroy
D000328:Adult; D050110:Bariatric Surgery; D002097:C-Reactive Protein / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007737:Kynurenine / Q000097:blood; D055442:Metabolome; D017378:Quinolinic Acid / Q000097:blood*; D012701:Serotonin / Q000097:blood; D014364:Tryptophan / Q000097:blood; D014977:Xanthurenates / Q000097:blood*
D014977:Xanthurenates; D012701:Serotonin; D007737:Kynurenine; C028330:xanthurenic acid; D014364:Tryptophan; D002097:C-Reactive Protein; D017378:Quinolinic Acid; D005947:Glucose