The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation Academic Article uri icon

  •  
  • Overview
  •  
  • Research
  •  
  • Identity
  •  
  • Additional Document Info
  •  
  • View All
  •  

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.

authors

  • Favennec, Marie
  • Hennart, Benjamin
  • Caiazzo, Robert
  • Leloire, Audrey
  • Yengo, Loïc
  • Verbanck, Marie
  • Arredouani, Abdelilah
  • Marre, Michel
  • Pigeyre, Marie Eva
  • Bessede, Alban
  • Guillemin, Gilles J
  • Chinetti, Giulia
  • Staels, Bart
  • Pattou, François
  • Balkau, Beverley
  • Allorge, Delphine
  • Froguel, Philippe
  • Poulain-Godefroy, Odile

publication date

  • October 2015