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Cited by 276

The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.

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

Favennec, Marie, Hennart, Benjamin, Caiazzo, Robert, Leloire, Audrey, Yengo, Loïc, Verbanck, Marie, Arredouani, Abdelilah, Marre, Michel, Pigeyre, Marie, Bessede, Alban, Guillemin, Gilles J., Chinetti, Giulia, Staels, Bart, Pattou, François, Balkau, Beverley, Allorge, Delphine, Froguel, Philippe, Poulain‐Godefroy, Odile·2015·Obesity
DOI 10.1002/oby.21199
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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.

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Metadata

Authors
Favennec, M., Hennart, B., Caiazzo, R., Leloire, A., Yengo, L., Verbanck, M., Arredouani, A., Marre, M., Pigeyre, M., Bessede, A., Guillemin, G. J., Chinetti, G., Staels, B., Pattou, F., Balkau, B., Allorge, D., Froguel, P., & Poulain‐Godefroy, O.
Venue
Obesity
Publisher
Wiley
Published
2015-09-08
Volume
23
Issue
10
Pages
2066-2074
ISSN
  • 1930-7381 (ISSN-L)
  • 1930-739X
DOI
10.1002/oby.21199
OpenAlex
W1816148962
Cited by
276
References
35
FWCI
11.70
Type
journal article
Language
en
Open access
closed

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