“Kynurenine switch” and obesity

Aim. To assess the concentrations of bacterial and eukaryotic metabolites mainly involved in indole, kynurenine, and serotonin pathways of tryptophan metabolism in a cohort of patients with obesity. Materials and methods. Using high-performance liquid chromatography with mass spectrometric detection...

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Main Authors: A. V. Shestopalov, O. P. Shatova, M. S. Karbyshev, A. M. Gaponov, N. E. Moskaleva, S. A. Appolonova, A. V. Tutelyan, V. V. Makarov, S. M. Yudin, S. A. Roumiantsev
Format: Article
Language:English
Published: Siberian State Medical University (Tomsk) 2022-01-01
Series:Бюллетень сибирской медицины
Subjects:
Online Access:https://bulletin.ssmu.ru/jour/article/view/4587
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author A. V. Shestopalov
O. P. Shatova
M. S. Karbyshev
A. M. Gaponov
N. E. Moskaleva
S. A. Appolonova
A. V. Tutelyan
V. V. Makarov
S. M. Yudin
S. A. Roumiantsev
author_facet A. V. Shestopalov
O. P. Shatova
M. S. Karbyshev
A. M. Gaponov
N. E. Moskaleva
S. A. Appolonova
A. V. Tutelyan
V. V. Makarov
S. M. Yudin
S. A. Roumiantsev
author_sort A. V. Shestopalov
collection DOAJ
description Aim. To assess the concentrations of bacterial and eukaryotic metabolites mainly involved in indole, kynurenine, and serotonin pathways of tryptophan metabolism in a cohort of patients with obesity. Materials and methods. Using high-performance liquid chromatography with mass spectrometric detection, the concentrations of several serum metabolites, such as kynurenine, kynurenic acid, anthranilic acid, xanthurenic acid, quinolinic acid, 5-hydroxyindole-3-acetate, tryptamine, serotonin, indole-3-lactate, indole-3-acetate, indole-3- butyrate, indole-3-carboxaldehyde, indole-3-acrylate, and indole-3-propionate, were analyzed in a cohort of obese patients compared with healthy volunteers.Results. It was found that serum levels of tryptophan metabolites of microbial and eukaryotic origin were significantly increased in obese patients. Therefore, the concentration of kynurenine in the blood serum in obese patients was 2,413 ± 855 nmol / l, while in healthy volunteers of the same age group, the level of kynurenine in the blood serum was 2,122 ± 863 nmol / l. In obese patients, two acids formed due to kynurenine metabolism; the concentrations of kynurenic and quinolinic acids were increased in the blood serum. The concentration of kynurenic acid in the blood serum in obese patients was 21.1 ± 9.26 nmol / l, and in healthy patients, it was 16.8 ± 8.37 nmol / l. At the same time, the level of quinolinic acid in the blood serum in obese patients was 73.1 ± 54.4 nmol / l and in healthy volunteers – 56.8 ± 34.1 nmol / l. Normally, the level of quinolinic acid is 3.4 times higher than the concentration of kynurenic acid, and in case of obesity, there is a comparable increase in these acids in the blood serum.From indole derivatives, mainly of microbial origin, the concentrations of indole-3-lactate, indole-3-butyrate, and indole-3-acetate were significantly increased in the blood serum of obese patients. In obese patients, the serum concentration of 5-hydroxyindole-3-acetate was elevated to 74.6 ± 75.8 nmol / l (in healthy volunteers – 59.4 ± 36.6 nmol / l); indole-3-lactate – to 523 ± 251 nmol / l (in healthy volunteers – 433 ± 208 nmol / l); indole-3-acetate – to 1,633 ± 1,166 nmol / l (in healthy volunteers – 1,186 ± 826 nmol / l); and indole-3-butyrate – to 4.61 ± 3.31 nmol / l (in healthy volunteers – 3.85 ± 2.51 nmol / l).Conclusion. In case of obesity, the utilization of tryptophan was intensified by both the microbiota population and the macroorganism. It was found that obese patients had higher concentrations of kynurenine, quinolinic and kynurenic acids, indole-3-acetate, indole-3-lactate, indole-3-butyrate, and 5-hydroxyindole-3-acetate. Apparently, against the background of increased production of proinflammatory cytokines by adipocytes in obese patients, the “kynurenine switch” was activated which contributed to subsequent overproduction of tryptophan metabolites involved in the immune function of the macroorganism.
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spelling doaj.art-5ed5bf8cd1024caebd973d64d94390552023-03-13T09:58:27ZengSiberian State Medical University (Tomsk)Бюллетень сибирской медицины1682-03631819-36842022-01-0120410311110.20538/1682-0363-2021-4-103-1112846“Kynurenine switch” and obesityA. V. Shestopalov0O. P. Shatova1M. S. Karbyshev2A. M. Gaponov3N. E. Moskaleva4S. A. Appolonova5A. V. Tutelyan6V. V. Makarov7S. M. Yudin8S. A. Roumiantsev9Национальный медицинский исследовательский центр (НМИЦ) Детской гематологии, онкологии и иммунологии имени Дмитрия Рогачева; Российский национальный исследовательский медицинский университет (РНИМУ) им. Н.И. ПироговаРоссийский национальный исследовательский медицинский университет (РНИМУ) им. Н.И. ПироговаРоссийский национальный исследовательский медицинский университет (РНИМУ) им. Н.И. ПироговаНациональный медицинский исследовательский центр (НМИЦ) Детской гематологии, онкологии и иммунологии имени Дмитрия РогачеваПервый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский университет)Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский университет)Центральный научно-исследовательский институт (НИИ) эпидемиологии Роспотребнадзора Российской Федерации (РФ)Центр стратегического планирования и управления медико-биологическими рисками здоровьюЦентр стратегического планирования и управления медико-биологическими рисками здоровьюРоссийский национальный исследовательский медицинский университет (РНИМУ) им. Н.И. ПироговаAim. To assess the concentrations of bacterial and eukaryotic metabolites mainly involved in indole, kynurenine, and serotonin pathways of tryptophan metabolism in a cohort of patients with obesity. Materials and methods. Using high-performance liquid chromatography with mass spectrometric detection, the concentrations of several serum metabolites, such as kynurenine, kynurenic acid, anthranilic acid, xanthurenic acid, quinolinic acid, 5-hydroxyindole-3-acetate, tryptamine, serotonin, indole-3-lactate, indole-3-acetate, indole-3- butyrate, indole-3-carboxaldehyde, indole-3-acrylate, and indole-3-propionate, were analyzed in a cohort of obese patients compared with healthy volunteers.Results. It was found that serum levels of tryptophan metabolites of microbial and eukaryotic origin were significantly increased in obese patients. Therefore, the concentration of kynurenine in the blood serum in obese patients was 2,413 ± 855 nmol / l, while in healthy volunteers of the same age group, the level of kynurenine in the blood serum was 2,122 ± 863 nmol / l. In obese patients, two acids formed due to kynurenine metabolism; the concentrations of kynurenic and quinolinic acids were increased in the blood serum. The concentration of kynurenic acid in the blood serum in obese patients was 21.1 ± 9.26 nmol / l, and in healthy patients, it was 16.8 ± 8.37 nmol / l. At the same time, the level of quinolinic acid in the blood serum in obese patients was 73.1 ± 54.4 nmol / l and in healthy volunteers – 56.8 ± 34.1 nmol / l. Normally, the level of quinolinic acid is 3.4 times higher than the concentration of kynurenic acid, and in case of obesity, there is a comparable increase in these acids in the blood serum.From indole derivatives, mainly of microbial origin, the concentrations of indole-3-lactate, indole-3-butyrate, and indole-3-acetate were significantly increased in the blood serum of obese patients. In obese patients, the serum concentration of 5-hydroxyindole-3-acetate was elevated to 74.6 ± 75.8 nmol / l (in healthy volunteers – 59.4 ± 36.6 nmol / l); indole-3-lactate – to 523 ± 251 nmol / l (in healthy volunteers – 433 ± 208 nmol / l); indole-3-acetate – to 1,633 ± 1,166 nmol / l (in healthy volunteers – 1,186 ± 826 nmol / l); and indole-3-butyrate – to 4.61 ± 3.31 nmol / l (in healthy volunteers – 3.85 ± 2.51 nmol / l).Conclusion. In case of obesity, the utilization of tryptophan was intensified by both the microbiota population and the macroorganism. It was found that obese patients had higher concentrations of kynurenine, quinolinic and kynurenic acids, indole-3-acetate, indole-3-lactate, indole-3-butyrate, and 5-hydroxyindole-3-acetate. Apparently, against the background of increased production of proinflammatory cytokines by adipocytes in obese patients, the “kynurenine switch” was activated which contributed to subsequent overproduction of tryptophan metabolites involved in the immune function of the macroorganism.https://bulletin.ssmu.ru/jour/article/view/4587микробиотатриптофаножирениекинурениныиндолыметаболический синдром
spellingShingle A. V. Shestopalov
O. P. Shatova
M. S. Karbyshev
A. M. Gaponov
N. E. Moskaleva
S. A. Appolonova
A. V. Tutelyan
V. V. Makarov
S. M. Yudin
S. A. Roumiantsev
“Kynurenine switch” and obesity
Бюллетень сибирской медицины
микробиота
триптофан
ожирение
кинуренины
индолы
метаболический синдром
title “Kynurenine switch” and obesity
title_full “Kynurenine switch” and obesity
title_fullStr “Kynurenine switch” and obesity
title_full_unstemmed “Kynurenine switch” and obesity
title_short “Kynurenine switch” and obesity
title_sort kynurenine switch and obesity
topic микробиота
триптофан
ожирение
кинуренины
индолы
метаболический синдром
url https://bulletin.ssmu.ru/jour/article/view/4587
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AT nemoskaleva kynurenineswitchandobesity
AT saappolonova kynurenineswitchandobesity
AT avtutelyan kynurenineswitchandobesity
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