The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation.
Obesity (Silver Spring)
; 23(10): 2066-74, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-26347385
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Quinurenina 3-Monooxigenasa
/
Quinurenina
/
Obesidad
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Obesity (Silver Spring)
Asunto de la revista:
CIENCIAS DA NUTRICAO
/
FISIOLOGIA
/
METABOLISMO
Año:
2015
Tipo del documento:
Article
País de afiliación:
Francia