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

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

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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.

Original languageEnglish
Pages (from-to)2066-2074
Number of pages9
JournalObesity
Volume23
Issue number10
DOIs
Publication statusPublished - 1 Oct 2015

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Kynurenine
Mixed Function Oxygenases
Obesity
Kynurenine 3-Monooxygenase
kynureninase
Indoleamine-Pyrrole 2,3,-Dioxygenase
Adipose Tissue
Macrophages
kynurenine-oxoglutarate transaminase
Adipocytes
Body Mass Index
Enzymes
Kynurenic Acid
Quinolinic Acid
Subcutaneous Fat
Tryptophan
Insulin Resistance
Cohort Studies
Anti-Inflammatory Agents
Cytokines

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

Cite this

Favennec, M., Hennart, B., Caiazzo, R., Leloire, A., Yengo, L., Verbanck, M., ... Poulain-Godefroy, O. (2015). The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation. Obesity, 23(10), 2066-2074. https://doi.org/10.1002/oby.21199

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.

In: Obesity, Vol. 23, No. 10, 01.10.2015, p. 2066-2074.

Research output: Contribution to journalArticle

Favennec, M, Hennart, B, Caiazzo, R, Leloire, A, Yengo, L, Verbanck, M, Arredouani, A, Marre, M, Pigeyre, M, Bessede, A, Guillemin, GJ, Chinetti, G, Staels, B, Pattou, F, Balkau, B, Allorge, D, Froguel, P & Poulain-Godefroy, O 2015, 'The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation', Obesity, vol. 23, no. 10, pp. 2066-2074. https://doi.org/10.1002/oby.21199
Favennec M, Hennart B, Caiazzo R, Leloire A, Yengo L, Verbanck M et al. The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation. Obesity. 2015 Oct 1;23(10):2066-2074. https://doi.org/10.1002/oby.21199
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. / The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation. In: Obesity. 2015 ; Vol. 23, No. 10. pp. 2066-2074.
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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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T1 - The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation

AU - Favennec, Marie

AU - Hennart, Benjamin

AU - Caiazzo, Robert

AU - Leloire, Audrey

AU - Yengo, Loïc

AU - Verbanck, Marie

AU - Arredouani, Abdelilah

AU - Marre, Michel

AU - Pigeyre, Marie

AU - Bessede, Alban

AU - Guillemin, Gilles J.

AU - Chinetti, Giulia

AU - Staels, Bart

AU - Pattou, François

AU - Balkau, Beverley

AU - Allorge, Delphine

AU - Froguel, Philippe

AU - Poulain-Godefroy, Odile

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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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