Нажмите на эту строку чтобы перейти к Новостям сайта "Русский врач"

Перейти
на сайт
журнала
"Врач"
Перейти на сайт журнала "Медицинская сестра"
Перейти на сайт журнала "Фармация"
Перейти на сайт журнала "Молекулярная медицина"
Перейти на сайт журнала "Вопросы биологической, медицинской и фармацевтической химии"
Журнал включен в российские и международные библиотечные и реферативные базы данных

ВАК (Россия)
РИНЦ (Россия)
Эко-Вектор (Россия)

RELATIONSHIP OF THE LEVELS OF TRYPTOFAN METABOLITES WITH ADIPOKINES AND MYOKINES IN PATIENTS WITH VARIOUS OBESITY PHENOTYPES

DOI: https://doi.org/10.29296/25877313-2023-03-05
Issue: 
3
Year: 
2023

O.P. Shatova
Ph.D. (Med.), Associate Professor of the Department of Biochemistry and Molecular Biology,
Pirogov Russian National Research Medical University (Moscow, Russia)
E-mail: shatova.op@gmail.com; ORCID 0000-0003-4265-1293
S.A. Appolonova
Ph.D. (Chem.), Head of the Center for Biopharmaceutical Analysis and Metabolomic Research,
Institute of Translational Medicine and Biotechnology,
First Moscow State Medical University (Sechenov University) (Moscow, Russia)
ORCID 0000-0002-7309-8913
S.A. Roumiantsev
Dr.Sc. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences,
Head of the Department of Oncology, Hematology and Radiation Therapy, Faculty of Pediatrics,
Pirogov Russian National Research Medical University (Moscow, Russia)
ORCID 0000-0002-7418-0222
A.V. Shestopalov
Dr.Sc. (Med.), Professor, Head of the Department of Biochemistry and Molecular Biology,
Pirogov Russian National Research Medical University (Moscow, Russia)
E-mail: al-shest@yandex.ru; ORCID 0000-0002-1428-7706

Relevance. In the last 10 years, there has been an active study of the system of conjugation of the metabolism of a macroorganism and its microbiome. The microbiotic conversion of tryptophan into biologically active signaling molecules is a potential regulatory mechanism by which the intestinal microbiota can change the metabolism of both intestinal cells and the entire macroorganism. However, the content of tryptophan metabolism metabolites in patients with metabolically healthy (MHO) and metabolically unhealthy obesity (MUHO), as well as the relationship of these metabolites with adipokines and myokines, has not yet been studied. Purpose of the study. To study the content of metabolites of tryptophan metabolism in the blood serum of obese patients and to evaluate the relationship between the content of adipokines and myokines and the content of tryptophan metabolism metabolites of bacterial and non-bacterial origin in the blood serum of patients with MSO and MNSO. Material and methods. 266 patients were examined, including 138 healthy non-obese volunteers and 128 obese patients, of whom two subgroups were formed: 30 patients with MHO and 41 patients with MUHO. Metabolite concentrations in blood and feces were determined using high performance liquid chromatography. Quantitative analysis of adipokines and myokines was performed by multiplex enzyme immunoassay. The content of metabolites of tryptophan metabolism in blood serum was assessed by high performance liquid chromatography with mass spectrometric detection. Results. For patients with obesity, an increase in the serum concentration of kynurenine, kynurenic and quinoline acids, indole-3-lactate, indole-3-butyrate and indole-3-acetate was established. Patients with MHO and MUHO were statistically significantly different only in terms of serum tryptamine concentration. Regardless of the presence/absence of metabolic disorders in obese patients, it has been established that xanthurenic and quinoline acids are interrelated with the concentration of myostatin in the blood serum. At the same time, for patients with MHO, it was shown that the serum concentration of the dominant catabolite of the indole pathway, indole-3-acetate, is interconnected with the content of insulin and leptin in the blood serum. Whereas in patients with MUHO, leptinemia is consistent with a high concentration of anthranilic acid in the blood serum, and hyperinsulinemia, on the contrary, is associated with a low concentration of indole-3-propionate in the blood serum.
Keywords: 
obesity
adipokines; myokines; tryptophan metabolites.
References: 
  1. Recinella L., Orlando G., Ferrante C., Chiavaroli A., Brunetti L., Leone Sh. Adipokines: New Potential Therapeutic Target for Obesi-ty and Metabolic, Rheumatic, and Cardiovascular Diseases. Front Physiol. 2020; 11: 1–32. DOI: 10.3389/fphys. 2020. 578966.
  2. Senesi P., Luzi L., Terruzzi I. Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions. Int J Mol Sci. 2020; 8(21): 8372. DOI: 10.3390/ijms21218372.
  3. Gonzalez-Gil A.M., Elizondo-Montemayor L. The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss. Nutrients, 2020; 12(6): 1899. DOI: 10.3390/nu12061899.
  4. Li F., Li Y., Duan Y., Hu C.A., Tang Y., Yin Y. Myokines and adipokines: Involvement in the crosstalk between skeletal muscle and adipose tissue. Cytokine Growth Factor Rev. 2017; 33: 73–82.
  5. Mallmann.N.H., Lima E.S., Lalwani P. Dysregulation of Tryptophan Catabolism in Metabolic Syndrome. Metab Syndr Relat Disord. 2018; 16: 135–142.
  6. Шестопалов А.В., Шатова О.П., Комарова Е.Ф., Румянцев С.А. Особенности метаболического сопряжения в системе «су-перорганизма» (хозяин-микробиота) Крымский журнал экспе-риментальной и клинической медицины. 2020; 10(2): 95–103. DOI: 10.37279/2224-6444-2020-10-2-95-103 (Shestopalov A.V., Shatova O.P., Komarova E.F., Rumjancev S.A. Osobennosti metabolicheskogo soprjazhenija v sisteme «superorganizma» (hozjain-mikrobiota) Krymskij zhurnal jeksperimental'noj i klinicheskoj mediciny. 2020; 10(2): 95–103. DOI: 10.37279/2224-6444-2020-10-2-95-103).
  7. Grewal S., Gubbi S., Fosam A., Sedmak C., Sikder S., Talluru H., Brown R.J., Muniyappa R. Metabolomic Analysis of the Effects of Leptin Replacement Therapy in Patients with Lipodystrophy. J Endocr Soc. 2019; 4(1): bvz022. DOI: 10.1210/jendso/bvz022.
  8. Calapai G., Corica F., Corsonello A., Sautebin L., Di R.M., Campo G.M., Buemi M., Mauro V.N., Caputi A.P. Leptin increases serotonin turnover by inhibition of brain nitric oxide synthesis. J Clin Invest. 1999; 104: 975–982.
  9. Seridi L., Leo G.C., Dohm G.L., Pories W.J., Lenhard J. Time course metabolome of Roux-en-Y gastric bypass confirms correlation between leptin, body weight and the microbiome. PLoS One; 2018; 13(5): e0198156. DOI: 10.1371/journal.pone.0198156.
  10. Kaneko I., Sabir M.S., Dussik C.M., Whitfield G.K., Karrys A., Hsieh J.C., Haussler M.R., Meyer M.B., Pike J.W., Jurutka P.W. 1,25-Dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: implication for behavioral influences of vitamin D. FASEB J. 2015; 29: 4023–4035.
  11. Li C., Meng F., Garza J.C., Liu J., Lei Y., Kirov S.A., Guo M., Lu X.Y. Modulation of depression-related behaviors by adiponectin AdipoR1 receptors in 5-HT neurons. Mol Psychiatry. 2020; 10: 1038/s41380-020-0649-0. DOI: 10.1038/s41380-020-0649-0.
  12. Pokusa M., Hlavacova N., Csanova A., Franklin M., Zorad S., Jezova D. Adipogenesis and aldosterone: a study in lean trypto-phan-depleted rats. Gen Physiol Biophys. 2016; 35: 379–386.
  13. Nakamura H., Jinzu H., Nagao K., Noguchi Y., Shimba N., Miyano H., Watanabe T., Iseki K. Plasma amino acid profiles are associated with insulin, C-peptide and adiponectin levels in type 2 diabetic patients. Nutr Diabetes. 2014; 4 (9): e133. doi: 10.1038/nutd.2014.32.
  14. Byun K., Lee S. The Potential Role of Irisin in Vascular Function and Atherosclerosis. Int J Mol Sci. 2020; 21(19): 7184. doi: 10.3390/ijms21197184.
  15. Dadvar S., Ferreira D., Cervenka I., Ruas J. The weight of nutrients: kynurenine metabolites in obesity and exercise. J Intern Med. 2018; 284(5): 519–533. DOI: 10.1111/joim.12830.
  16. Knudsen C., Neyrinck A., Lanthier N. Microbiota and nonalcoholic fatty liver disease: promising prospects for clinical interventions? Curr.Opin.Clin.Nutr.Metab Care. 2019; 22(5): 393–400. doi: 10.1097/MCO.0000000000000584.
  17. Bhattarai Y., Williams B.B., Battaglioli E.J. Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion. Cell Host Microbe. 2018; 23(6): 775–785e5. doi:10.1016/j.chom.2018.05.004.
  18. Zhao Z., Xin F., Xue Y. Indole-3-propionic acid inhibits gut dysbiosis and endotoxin leakage to attenuate steatohepatitis in rats. Exp. Mol. Med. 2019; 51 (9): 1–14. DOI: 10.1038/s12276-019-0304-5.
  19. Li S.N., Wu J.F. TGF-beta/SMAD signaling regulation of mesen-chymal stem cells in adipocyte commitment. Stem Cell Res Ther. 2020; 11: 41.
  20. Ge X., Sathiakumar D., Lua B.J., Kukreti H., Lee M., McFarlane C. Myostatin signals through miR-34a to regulate Fndc5 expression and browning of white adipocytes. Int J Obes (Lond). 2017; 41: 137–148.
  21. Naiemian S., Naeemipour M., Zarei M., Lari N.M., Gohari A., Behroozikhah M.R., Heydari H., Miri M. Serum concentration of asprosin in new-onset type 2 diabetes. Diabetol Metab Syndr. 2020; 12: 65. DOI: 10.1186/s13098-020-00564-w.
  22. Chiavaroli A., Recinella L., Ferrante C., Martinotti S., Vacca M., Brunetti L., Orlando G., Leone S. Effects of central fibroblast growth factor 21 and irisin in anxiety-like behavior. J Biol Regul Homeost Agents. 2017; 31: 797–802.