The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation. (8th September 2015)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Obesity. Volume 23:Number 10(2015:Oct.)
• Page Start: 2066
• Page End: 2074
• Publication Date: 2015-09-08
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.21199
• Languages: English
• ISSNs: 1930-7381

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="oby21199-sec-0001" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="oby21199-sec-0002" sec-type="section"> <title>Methods</title> <p>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 (<italic>n</italic> = 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.</p> </sec> <sec id="oby21199-sec-0003" sec-type="section"> <title>Results</title> <p>In the D.E.S.I.R. cohort, kynurenine levels were positively associated with body mass index (BMI) (<italic>P</italic> = 4.68 × 10<sup>−19</sup>) and with a higher HOMA2‐IR insulin resistance index (<italic>P</italic> = 6.23 × 10<sup>−4</sup>). The levels of kynurenine, kynurenic acid, and quinolinic acid were associated with higher BMI (<italic>P</italic> < 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 (<italic>P</italic> < 0.05), and their expression was induced by proinflammatory cytokines in human primary adipocytes (<italic>P</italic> < 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 (<italic>P</italic> < 0.05).</p> </sec> <sec id="oby21199-sec-0004" sec-type="section"> <title>Conclusions</title> <p>In the context of obesity, the presence of macrophages in adipose tissue may contribute to diverting KP toward KMO activation.</p> </sec> </abstract>