The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation

Favennec, Marie, Hennart, Benjamin, Caiazzo, Robert, Leloire, Audrey, Yengo, Loic, Verbanck, Marie, Arredouani, Abdelilah, Marre, Michel, Pigeyre, Marie, Bessede, Alban, Guillemin, Gilles J., Chinetti, Giulia, Staels, Bart, Pattou, Francois, Balkau, Beverley, Allorge, Delphine, Froguel, Philippe and Poulain-Godefroy, Odile (2015) The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation. Obesity, 23 10: 2066-2074. doi:10.1002/oby.21199


Author Favennec, Marie
Hennart, Benjamin
Caiazzo, Robert
Leloire, Audrey
Yengo, Loic
Verbanck, Marie
Arredouani, Abdelilah
Marre, Michel
Pigeyre, Marie
Bessede, Alban
Guillemin, Gilles J.
Chinetti, Giulia
Staels, Bart
Pattou, Francois
Balkau, Beverley
Allorge, Delphine
Froguel, Philippe
Poulain-Godefroy, Odile
Title The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation
Journal name Obesity   Check publisher's open access policy
ISSN 1930-739X
1930-7381
Publication date 2015-10-01
Year available 2015
Sub-type Article (original research)
DOI 10.1002/oby.21199
Open Access Status Not yet assessed
Volume 23
Issue 10
Start page 2066
End page 2074
Total pages 9
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Objective
This study characterized the kynurenine pathway (KP) in human obesity by evaluating circulating levels of kynurenines and the expression of KP enzymes in adipose tissue.

Methods
Tryptophan and KP metabolite levels were measured in serum of individuals from the D.E.S.I.R. cohort (case–cohort study: 212 diabetic, 836 randomly sampled) and in women with obesity, diabetic or normoglycemic, from the ABOS cohort (n = 100). KP enzyme gene expressions were analyzed in omental and subcutaneous adipose tissue of women from the ABOS cohort, in human primary adipocytes and in monocyte-derived macrophages.

Results
In the D.E.S.I.R. cohort, kynurenine levels were positively associated with body mass index (BMI) (P = 4.68 × 10−19) and with a higher HOMA2-IR insulin resistance index (P = 6.23 × 10−4). The levels of kynurenine, kynurenic acid, and quinolinic acid were associated with higher BMI (P < 0.05). The expression of several KP enzyme genes (indoleamine 2,3-dioxygenase 1 [IDO1], kynureninase [KYNU], kynurenine 3-monooxygenase [KMO], and kynurenine aminotransferase III [CCBL2]) was increased in the omental adipose tissue of women with obesity compared to lean (P < 0.05), and their expression was induced by proinflammatory cytokines in human primary adipocytes (P < 0.05), except for KMO that is not expressed in these cells. The expressions of IDO1, KYNU, KMO, and CCBL2 were higher in proinflammatory than in anti-inflammatory macrophages (P < 0.05).

Conclusions
In the context of obesity, the presence of macrophages in adipose tissue may contribute to diverting KP toward KMO activation.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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