“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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Siberian State Medical University (Tomsk)
2022-01-01
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| Series: | Бюллетень сибирской медицины |
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| 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. |
| format | Article |
| id | doaj-art-5ed5bf8cd1024caebd973d64d9439055 |
| institution | DOAJ |
| issn | 1682-0363 1819-3684 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Siberian State Medical University (Tomsk) |
| record_format | Article |
| series | Бюллетень сибирской медицины |
| spelling | doaj-art-5ed5bf8cd1024caebd973d64d94390552025-08-20T03:02:04ZengSiberian 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. Roumiantsev9Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology; Pirogov Russian National Research Medical UniversityPirogov Russian National Research Medical UniversityPirogov Russian National Research Medical UniversityDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and ImmunologyI.M. Sechenov First Moscow State Medical UniversityI.M. Sechenov First Moscow State Medical UniversityCentral Research Institute of Epidemiology of the Federal Service for Surveillance on Consumer Rights Protection and Human Well-beingCenter for Strategic Planning and Management of Biomedical Health RisksCenter for Strategic Planning and Management of Biomedical Health RisksPirogov Russian National Research Medical UniversityAim. 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/4587microbiotatryptophanobesitykynureninesindolesmetabolic syndrome |
| 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 microbiota tryptophan obesity kynurenines indoles metabolic syndrome |
| 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 | microbiota tryptophan obesity kynurenines indoles metabolic syndrome |
| url | https://bulletin.ssmu.ru/jour/article/view/4587 |
| work_keys_str_mv | AT avshestopalov kynurenineswitchandobesity AT opshatova kynurenineswitchandobesity AT mskarbyshev kynurenineswitchandobesity AT amgaponov kynurenineswitchandobesity AT nemoskaleva kynurenineswitchandobesity AT saappolonova kynurenineswitchandobesity AT avtutelyan kynurenineswitchandobesity AT vvmakarov kynurenineswitchandobesity AT smyudin kynurenineswitchandobesity AT saroumiantsev kynurenineswitchandobesity |