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Obesity (Silver Spring). 2015 Oct;23(10):2066-74. doi: 10.1002/oby.21199. Epub 2015 Sep 8.

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

Favennec M1,2,3,4,5, Hennart B2,5,6, Caiazzo R2,4,5,7, Leloire A1,2,3,4, Yengo L1,2,3,4, Verbanck M1,2,3,4, Arredouani A8, Marre M9, Pigeyre M2,4,5,7, Bessede A10, Guillemin GJ11, Chinetti G2,3,4,12, Staels B2,3,4,12, Pattou F2,4,5,7, Balkau B13, Allorge D2,5,6, Froguel P1,2,3,4,5,14, Poulain-Godefroy O1,2,3,4.

Author information

  • 1CNRS UMR 8199, Lille, France.
  • 2University of Lille, Lille, France.
  • 3Institut Pasteur De Lille, Lille, France.
  • 4European Genomic Institute for Diabetes (EGID), Lille, France.
  • 5CHRU De Lille, Lille, France.
  • 6EA4483, Lille, France.
  • 7INSERM UMR 1190, Lille, France.
  • 8Qatar Biomedical Research Institute, Qatar Foundation, Doha, Qatar.
  • 9INSERM U872, Paris, France.
  • 10Immusmol, Pessac, France.
  • 11Neuroinflammation Group, Macquarie University, Sydney, New South Wales, Australia.
  • 12INSERM UMR 1011, Lille, France.
  • 13INSERM UMRS 1018, Villejuif, France.
  • 14Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK.

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.

PMID:
26347385
DOI:
10.1002/oby.21199
[PubMed - indexed for MEDLINE]
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