ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet13140ometendo-13140Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESИммуномодулирующее влияние капсаициноидов при метавоспалении у крыс линии Wistar с алиментарным ожирениемImmunomodulatory effect of capsaicinoids on metainflammation in Wistar rats with nutritional obesityhttps://orcid.org/0000-0002-0035-3629ТрушинаЭ. Н.TrushinaE. N.

Трушина Элеонора Николаевна, к.м.н., заведующая лабораторией иммунологии 

109240, г. Москва, Устьинский проезд, д. 2/14

 

Eleonora N. Trushina PhD

109240, Moscow, Ustinsky proezd, 2/14

trushina@ion.ruhttps://orcid.org/0000-0001-7149-2485РигерН. А.RigerN. A.

Ригер Николай Александрович, д.м.н., профессор, главный специалист лаборатории иммунологии

Москва

Nikolay A. Riger MD, PhD, Professor

Moscow

rieger_63@mail.ruhttps://orcid.org/0000-0001-7231-9377МустафинаО. К.MustafinaO. K.

Мустафина Оксана Константиновна, к.м.н., старший научный сотрудник лаборатории иммунологии

Москва

Oxana K. Mustafin PhD

Moscow

mustafina@ion.ruhttps://orcid.org/0000-0001-6087-6918ТимонинА. Н.TimoninA. N.

Тимонин Андрей Николаевич, к.б.н., научный сотрудник лаборатории иммунологии

Москва

Andrey N.Timonin PhD

Moscow

andrey8407@mail.ruhttps://orcid.org/0000-0003-4567-9347АксеновИ. В.AksenovI. V.

Аксенов Илья Владимирович, к.м.н., ведущий научный сотрудник лаборатории энзимологии

Москва

Andrey N.Timonin PhD

Moscow

ilyaaksenoff@yandex.ruhttps://orcid.org/0000-0002-4164-8992ТутельянВ. А.TutelyanV. A.

Тутельян Виктор Александрович, академик РАН, д.м.н., профессор, научный руководитель 

Москва

Victor A. Tutelyan, MD, PhD, D.Sc., Professor, Academician of the RAS

Moscow

tutelyan@ion.ruФГБУН Федеральный исследовательский центр питания, биотехнологии и безопасности пищиРоссияFederal Research Centre of Nutrition, Biotechnology and Food SafetyRussian FederationФГБУН Федеральный исследовательский центр питания, биотехнологии и безопасности пищи; Федеральное государственное автономное образовательное учреждение высшего образования Первый московский государственный медицинский университет им. И.М. Сеченова Минздрава РФ (Сеченовский Университет); Федеральное государственное автономное образовательное учреждение высшего образования Российский университет дружбы народов им. Патриса ЛумумбыРоссияFederal Research Centre of Nutrition, Biotechnology and Food Safety; I.M. Sechenov First Moscow State Medical University (Sechenov University); Peoples’ Friendship University of Russia named after Patrice LumumbaRussian Federation202514022026224350358Copyright © Трушина Э.Н., Ригер Н.А., Мустафина О.К., Тимонин А.Н., Аксенов И.В., Тутельян В.А., 20262026Трушина Э.Н., Ригер Н.А., Мустафина О.К., Тимонин А.Н., Аксенов И.В., Тутельян В.А.Trushina E.N., Riger N.A., Mustafina O.K., Timonin A.N., Aksenov I.V., Tutelyan V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/13140Обоснование

Обоснование. Ожирение и избыточная масса тела занимают одно из ведущих мест в структуре заболеваемости населения всего мира. Особую актуальность приобретает задача разработки эффективных методов лечения данной патологии, в том числе диетотерапии с применением биологически активных веществ, обладающих антиоксидантными и противовоспалительными свойствами.

Цель — изучение влияния капсаициноидов на иммунный статус на модели алиментарного ожирения у крыс.

Материалы и методы

Материалы и методы. Исследование проводили на самцах крыс линии Wistar, которые были рандомизированы по массе тела на 3 группы (по 10 животных, исходная масса тела — 350±10 г). Крысы получали полусинтетический стандартный рацион (группа 1) и высококалорийный холинодефицитный рацион (ВКХДР) (группы 2 и 3). Животным внутрижелудочно вводили (3,33 мл/кг массы тела) 3 раза в неделю подсолнечное масло (группы 1 и 2) или экстракт острого стручкового перца (капсаицин — 59%, дигидрокапсаицин — 31%, нордигидрокапсаицин — 4%) в подсолнечном масле (группа 3) в разовой дозе 15 мг капсаициноидов/кг массы тела. Гематологические исследования выполняли на гематологическом анализаторе Coulter ACT TM 5 diff OV (Beckman Coulter, США). Изучение субпопуляционного состава лимфоцитов проводили на проточном цитофлуориметре FC-500 (Beckman Coulter, США). Содержание цитокинов в плазме крови крыс определяли методом мультиплексного иммуноанализа на анализаторе Luminex 200 (Luminex Corporation, США).

Результаты

Результаты. У крыс 2-й группы по сравнению с контрольной выявлено наличие нейтрофильного лейкоцитоза (1,20±0,13 vs 0,72±0,07 х10⁹ /л; р< 0,05). Исследование субпопуляционного состава лимфоцитов у крыс 2-й группы выявило повышение относительного содержания Т-хелперов (61,41±1,31 vs 53,30±3,25%; р < 0,05) и величины иммунорегуляторного индекса (ИРИ): (1,94±0,15 vs 1,55±0,14; 0,05<р < 0,10) по сравнению с показателями контрольной группы. Введение крысам 3-й группы капсаициноидов привело к нормализации данных показателей. У животных 2-й группы обнаружено достоверное повышение в плазме крови уровней цитокинов: IFN-γ, IL-1β, IL-5, IL-10, IL-17A, и MCP-1 и снижение содержания IL-2 и TNF-α по сравнению с контрольной группой. Капсаициноиды, вводимые крысам 3-й группы, обеспечили возрастание (p < 0,05) содержания IL-12(p70) и MIP-2 по сравнению со 2-й и 1-й группами. За счет этого влияния значимо увеличилась медиана соотношения уровня IL-10 к IL-12(p70) (1,52 vs 0,29 и 0,23), но оставалась достоверно меньше контрольного значения медиана IL-10/17A (1,54 vs 3,07).

Заключение

Заключение. Установлено противовоспалительное действие капсаициноидов экстракта острого стручкового перца при алиментарном ожирении у крыс.

ВACKGROUND

ВACKGROUND. Obesity and overweight occupy one of the leading places in the structure of morbidity in the population around the world. Of particular relevance is the task of developing effective methods for treating this pathology, including diet therapy using biologically active substances with antioxidant and anti-inflammatory properties.

AIM was to study the effect of capsaicinoids on the immune status in a model of nutritional obesity in rats.

MATERIALS AND METHODS

MATERIALS AND METHODS. The study was carried out on male Wistar rats, which were randomized by body weight into 3 groups (10 animals each, initial body weight 350±10 g). The rats received a semisynthetic standard diet (group 1) and a high-calorie choline-deficient diet (HCChDD) (groups 2 and 3). Animals were intragastrically administered (3.33 ml/kg body weight) 3 times a week sunflower oil (groups 1 and 2) or hot pepper extract (capsaicin — 59%, dihydrocapsaicin — 31%, nordihydrocapsaicin — 4%) in sunflower oil (group 3) in a single dose of 15 mg capsaicinoids/kg body weight. Hematological studies were performed on a Coulter ACT TM 5 diff OV hematological analyzer (Beckman Coulter, USA). The study of the subpopulation composition of lymphocytes was carried out using a flow cytometer FC-500 (Beckman Coulter, USA). The content of cytokines in the blood plasma of rats was determined by multiplex immunoassay using a Luminex 200 analyzer (Luminex Corporation, USA).

RESULTS

RESULTS. In rats of the 2nd group, compared with the control, the presence of neutrophilic leukocytosis (1.20±0.13 vs 0.72±0.07 x109/l; p < 0.05). A study of the subpopulation composition of lymphocytes in rats of the 2nd group revealed an increase in the relative content of T-helpers (61.41±1.31 vs 53.30±3.25%; p < 0.05) and the value of the immunoregulatory index (IRI): (1.94±0.15 vs 1.55±0.14; 0.05<p < 0.10) compared to the control group. Administration of capsaicinoids to rats of the 3rd group led to the normalization of these indicators. In animals of the 2nd group, a significant increase in the blood plasma levels of cytokines was found: IFN-γ, IL-1β, IL-5, IL-10, IL-17A, and MCP-1 and a decrease in the content of IL-2 and TNF-α according to compared with the control group. Capsaicinoids administered to rats of group 3 provided an increase (p < 0.05) in the levels of: IL-2, IL-4, IL-5, IL-6, IL-10, IL-17A, MIP-1α and TNF-α and a decrease (p < 0.05) in the content of IL-12(p70) and MIP-2 compared to groups 2 and 1. Due to this influence, the median ratio of the level of IL-10 to IL-12(p70) increased significantly (1.52 vs 0.29 and 0. 23), but the median IL-10/17A remained significantly lower than the control value (1.54 vs 3.07).

CONCLUSION

CONCLUSION. The anti-inflammatory effect of capsaicinoids in the extract of hot capsicum on nutritional obesity in rats has been established.

алиментарное ожирениеметавоспалениекапсаициноидыклеточный иммунитетцитокиныnutritional obesitymetainflammationcapsaicinoidscellular immunitycytokinesРабота по подготовке рукописи проведена за счет средств субсидии на выполнение государственного задания в рамках Программы фундаментальных научных исследований (тема № FGMF-2022-0003).ReferencesO’Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat. Rev. Immunol. 2016;16(9):553–565. doi: https://doi.org/10.1038/nri.2016.70O’Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists // Nat. Rev. Immunol. 2016;16 (9):553–565. doi: https://doi.org/ 10.1038/nri.2016.70.Hotamisligil GS. Foundations of Immunometabolism and Implications for Metabolic Health and Disease. Immunity. 2017;47(3):406-420. doi: https://doi.org/10.1016/j.immuni.2017.08.009Hotamisligil GS. Foundations of Immunometabolism and Implications for Metabolic Health and Disease. Immunity. 2017;47(3):406-420. doi: https://doi.org/10.1016/ j.immuni.2017.08.009Makowski L, Chaib M, Rathmell JC. Immunometabolism: From basic mechanisms to translation. Immunol Rev. 2020;295(1):5-14. doi: https://doi.org/10.1111/imr.12858Makowski L, Chaib M, Rathmell JC. Immunometabolism: From basic mechanisms to translation. Immunol Rev. 2020;295(1): 5-14. doi: https://doi.org/10.1111/imr.12858.Kawai T, Autieri MV, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol Cell Physiol. 2021;320(3):375-391. doi: https://doi.org/10.1152/ajpcell.00379.2020Kawai T, Autieri MV, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol Cell Physiol. 2021;320(3):375-391. doi: https://doi.org/10.1152/ajpcell.00379.2020.Wu H, Ballantyne CM. Metabolic Inflammation and Insulin Resistance in Obesity.Circ Res. 2020;126(11):1549-1564. doi: https://doi.org/10.1161/CIRCRESAHA.119.315896Wu H, Ballantyne CM. Metabolic Inflammation and Insulin Resistance in Obesity. Circ Res. 2020; 126(11):1549-1564. doi: https://doi.org/10.1161/ CIRCRESAHA.119.315896.Dunbar CL, Aukema HM, Calder PC, et al. Nutrition and immunity: perspectives on key issues and next steps. Appl Physiol Nutr Metab. 2023;48(7):484-497. doi: https://doi.org/10.1139/apnm-2022-0276Dunbar CL, Aukema HM, Calder PC, et al. Nutrition and immunity: perspectives on key issues and next steps. Appl Physiol Nutr Metab. 2023;48(7):484-497. doi: https://doi.org/10.1139/apnm-2022-0276.Li Y, Wang F, Imani S, et al.. Natural Killer Cells: Friend or Foe in Metabolic Diseases? Front Immunol. 2021;12: 614429. doi: https://doi.org/10.3389/fimmu.2021.614429Li Y, Wang F, Imani S, et al.. Natural Killer Cells: Friend or Foe in Metabolic Diseases? Front Immunol. 2021;12: 614429. doi: https://doi.org/10.3389/fimmu.2021.614429.Shi J, Fan J, Su Q, et al. Cytokines and Abnormal Glucose and Lipid Metabolism. Front Endocrinol (Lausanne). 2019;10:703. doi: https://doi.org/10.3389/fendo.2019.00703. eCollection 2019Shi J, Fan J, Su Q, et al. Cytokines and Abnormal Glucose and Lipid Metabolism. Front Endocrinol (Lausanne). 2019;10:703. doi: https://doi.org/10.3389/fendo.2019.00703. eCollection 2019.Zheng J, Zheng S, Feng Q, et al. Dietary capsaicin and its antiobesity potency: from mechanism to clinical implications. Biosci Rep. 2017;37(3):BSR20170286. doi: https://doi.org/10.1042/BSR20170286Zheng J, Zheng S, Feng Q, et al. Dietary capsaicin and its anti-obesity potency: from mechanism to clinical implications. Biosci Rep. 2017;37(3):BSR20170286. doi: https://doi.org/10.1042/BSR20170286.Li R, Lan Y, Chen C, et al. Anti-obesity effects of capsaicin and the underlying mechanisms: a review. Food & Function. 2020;11(9):7356-7370. doi: https://doi.org/10.1039/D0FO01467BLi R, Lan Y, Chen C, et al. Anti-obesity effects of capsaicin and the underlying mechanisms: a review. Food & Function. 2020;11(9): 7356-7370. doi: https://doi.org/10.1039/D0FO01467BO’Neill J, Brock C, Olesen AE, et al. Unravelling the mystery of capsaicin: a tool to understand and treat pain. Pharmacol Rev. 2012;64:939–971. doi: https://doi.org/10.1124/pr.112.006163O'Neill J, Brock C, Olesen AE, et al. Unravelling the mystery of capsaicin: a tool to understand and treat pain. Pharmacol Rev. 2012;64:939–971. doi: https://doi.org/ 10.1124/pr.112.006163.Periferakis AT, Periferakis A, Periferakis K, et al. Antimicrobial Properties of Capsaicin: Available Data and Future Research Perspectives. Nutrients. 2023;15(19):4097. doi: https://doi.org/10.3390/nu15194097Periferakis AT, Periferakis A, Periferakis K, et al. Antimicrobial Properties of Capsaicin: Available Data and Future Research Perspectives. Nutrients. 2023;15(19):4097. doi: 10.3390/nu15194097Lu M, Chen C; Lan Y. et al. Capsaicin-the major bioactive ingredient of chili peppers: Bio-efficacy and delivery systems. Food Funct. 2020;11:2848–2860. doi: https://doi.org/10.1039/d0fo00351dLu M, Chen C; Lan Y. et al. Capsaicin-the major bioactive ingredient of chili peppers: Bio-efficacy and delivery systems. Food Funct. 2020;11:2848–2860. doi: https://doi.org/ 10.1039/d0fo00351d.Thornton T, Mills D, Bliss E. Capsaicin: A Potential Treatment to Improve Cerebrovascular Function and Cognition in Obesity and Ageing. Nutrients. 2023;15(6):1537. doi: https://doi.org/10.3390/nu15061537Thornton T, Mills D, Bliss E. Capsaicin: A Potential Treatment to Improve Cerebrovascular Function and Cognition in Obesity and Ageing. Nutrients. 2023;15(6):1537. doi: 10.3390/nu15061537Xiang Y, Xu X, Zhang T, et al. Beneficial effects of dietary capsaicin in gastrointestinal health and disease. Exp Cell Res. 2022;417(2):113227. doi: https://doi.org/10.1016/j.yexcr.2022.113227Xiang Y, Xu X, Zhang T, et al. Beneficial effects of dietary capsaicin in gastrointestinal health and disease. Exp Cell Res. 2022;417(2):113227. doi: 10.1016/j.yexcr.2022.113227. Epub 2022 May 27.Rosca AE, Iesanu MI, Zahiu CDM, et al. Capsaicin and Gut Microbiota in Health and Disease. Molecules. 2020; 25(23):5681. doi: https://doi.org/10.3390/molecules25235681Rosca AE, Iesanu MI, Zahiu CDM, et al. Capsaicin and Gut Microbiota in Health and Disease. Molecules. 2020; 25(23):5681. doi: 10.3390/molecules25235681.Gong T, Zhou Y, Zhang L, et al. Capsaicin combined with dietary fiber prevents high-fat diet associated aberrant lipid metabolism by improving the structure of intestinal flora. Food Sci Nutr. 2022;11(1):114-125. doi: https://doi.org/10.1002/fsn3.3043. eCollection 2023Gong T, Zhou Y, Zhang L, et al. Capsaicin combined with dietary fiber prevents high-fat diet associated aberrant lipid metabolism by improving the structure of intestinal flora. Food Sci Nutr. 2022;11(1):114-125. doi: 10.1002/fsn3.3043. eCollection 2023Shanmugham V. and Subban R. Comparison of the Anti-Obesity Effect of Enriched Capsanthin and Capsaicin from Capsicum annuum L. Fruit in Obesity-Induced C57BL/6J Mouse Model. Food Technol Biotechnol. 2022:60(2):202–212. doi: https://doi.org/10.17113/ftb.60.02.22.7376Shanmugham V. and Subban R. Comparison of the Anti-Obesity Effect of Enriched Capsanthin and Capsaicin from Capsicum annuum L. Fruit in Obesity-Induced C57BL/6J Mouse Model. Food Technol Biotechnol. 2022:60(2):202–212. doi: https://doi.org/ 10.17113/ftb.60.02.22.7376Трушина Э.Н., Ригер Н.А., Мустафина О.К. и др. Влияние карнозина и α-липоевой кислоты на апоптоз гепатоцитов и цитокиновый профиль при индуцированной жировой дистрофии печени у крыс линии Вистар. // Вопросы питания. — 2020. — Т. 89. — № 5 — С. 6-16. doi: https://www.doi.org/10.24411/0042-8833-2020-10061Trushina EN, Riger NA, Mustafina OK et al.. Effect of carnosine and α-lipoic acid on hepatocyte apoptosis and the cytokine profile in induced fatty liver disease in Wistar rats. Voprosy pitaniia [Problems of Nutrition]. 2020;89(5):6–16. (In Russ).] doi: https://www.doi.org/10.24411/0042-8833-2020-10061.Руководство по экспериментальному (доклиническому) изучению новых фармакологических веществ / Под ред. Хабриева Р.У. 2-е издание, перераб. и доп. – М.: ОАО «Издательство «Медицина»; 2005.Manual on experimental (preclinical) study of new pharmacological substances. Ed by Khabriev RU. 2nd edition, revision and supplement. Moscow: JSC "Izdatelstvo "Medicine"; 2005. (In Russ).]Bley K, Boorman G, Mohammad B, et al. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol Pathol. 2012;40(6):847-873. doi: https://doi.org/10.1177/0192623312444471Bley K, Boorman G, Mohammad B, et al. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol Pathol. 2012;40(6):847-873. doi: https://doi.org/10.1177/0192623312444471Lejeune MP, Kovacs EM, Westerterp-Plantenga MS. Effect of capsaicin on substrate oxidation and weight maintenance after modest body-weight loss in human subjects. Br J Nutr. 2003; 90(3):651-659. doi: https://doi.org/10.1079/bjn2003938.Lejeune MP, Kovacs EM, Westerterp-Plantenga MS. Effect of capsaicin on substrate oxidation and weight maintenance after modest body-weight loss in human subjects. Br J Nutr. 2003; 90(3):651-659. doi: https://doi.org/10.1079/bjn2003938.Szallasi A. Capsaicin for Weight Control: «Exercise in a Pill» (or Just Another Fad)? Pharmaceuticals (Basel). 2022;15(7):851. doi: https://doi.org/10.3390/ph15070851Szallasi A. Capsaicin for Weight Control: "Exercise in a Pill" (or Just Another Fad)? Pharmaceuticals (Basel). 2022;15(7):851. doi: https://doi.org/10.3390/ph15070851Cable J, Rathmell JC, Pearce EL, et al. Immunometabolism at the crossroads of obesity and cancer-a Keystone Symposia report. Annals of the New York Academy of Sciences. 2023;1523(1):38–50. doi: https://doi.org/10.1111/nyas.14976Cable J, Rathmell JC, Pearce EL, et al. Immunometabolism at the crossroads of obesity and cancer-a Keystone Symposia report. Annals of the New York Academy of Sciences. 2023;1523(1):38–50. doi:https://doi.org/10.1111/nyas.14976Ярец Ю.И. Интерпретация результатов иммунограммы. — Гомель: ГУ «Республиканский научно-практический центр радиационной медицины и экологии человека»; 2020. https://www.rcrm.by/upload/science/posob_doctor/2020-17.pdfYarets Yu I. Interpretation of immunogram results. Gomel: Republican Scientific and Practical Center for Radiation Medicine and Human Ecology; 2020. (In Russ).] doi: https://www.rcrm.by/upload/science/posob_doctor/2020-17.pdfRomantsova TI, Sych YP. Immunometabolism and metainflammation in obesity. Obesity and metabolism. 2019;16(4):3-17. doi: https://doi.org/10.14341/omet12218Romantsova TI, Sych YP. Immunometabolism and metainflammation in obesity. Obesity and metabolism. 2019;16(4):3-17. doi: https://doi.org/10.14341/omet12218Monserrat-Mesquida M, Quetglas-Llabrés M, Capó X, et al. Metabolic Syndrome is Associated with Oxidative Stress and Proinflammatory State. Antioxidants (Basel). 2020;9(3):236. doi: https://doi.org/10.3390/antiox9030236Monserrat-Mesquida M, Quetglas-Llabrés M, Capó X, et al. Metabolic Syndrome is Associated with Oxidative Stress and Proinflammatory State. Antioxidants (Basel). 2020;9(3):236. doi: 10.3390/antiox9030236.Lee YS, Li P, Huh JY, et al. Inflammation Is Necessary for Long-Term but Not Short-Term High-Fat Diet–Induced Insulin Resistance. Diabetes. 2011;60(10):2474–2483. doi: https://doi.org/10.2337/db11-0194Lee YS, Li P, Huh JY, et al. Inflammation Is Necessary for Long-Term but Not Short-Term High-Fat Diet–Induced Insulin Resistance. Diabetes. 2011;60(10):2474–2483. doi: https://doi.org/10.2337/db11-0194Fahed G, Aoun L, Bou Zerdan M, et al. Metabolic Syndrome: Updates on Pathophysiology and Management in 2021. Int. J. Mol. Sci. 2022;23:786. doi: https://doi.org/10.3390/ijms23020786.Fahed G, Aoun L, Bou Zerdan M, et al. Metabolic Syndrome: Updates on Pathophysiology and Management in 2021. Int. J. Mol. Sci. 2022;23:786. doi: https://doi.org/10.3390/ ijms23020786.Shi J, Fan J, Su Q and Yang Z. Cytokines and Abnormal Glucose and Lipid Metabolism. Front. Endocrinol. 2019;10: 703. doi: https://doi.org/10.3389/fendo.2019.00703Shi J, Fan J, Su Q and Yang Z. Cytokines and Abnormal Glucose and Lipid Metabolism. Front. Endocrinol. 2019;10: 703. DOI: https://doi.org/10.3389/fendo.2019.00703Ригер Н.А., Трушина Э.Н., Мустафина О.К. и др. Патогенетические механизмы развития гематологических нарушений при индуцированной жировой дистрофии печени у крыс линии Wistar и оценка регуляторного влияния карнозина и α-липоевой кислоты. // Вопросы питания. — 2021. — Т. 90. — № 3. — С. 6–19. doi: https://doi.org/10.33029/0042-8833-2021-90-3-6-19Rieger N.A., Trushina E.N., Mustafina O.K, et al. Pathogenetic mechanisms of the development of hematological disorders in induced fatty liver dystrophy in Wistar rats and assessment of the regulatory effect of carnosine and α-lipoic acid. Voprosy pitaniia [Problems of Nutrition]. 2021;90(3):6–16. (In Russ).] doi: https://doi.org/10.33029/0042-8833-2021-90-3-6-19Reinhold D, Ansorge S, Schleicher ED. Elevated glucose levels stimulate transforming growth factor-beta 1 (TGF-beta 1), suppress interleukin IL-2, IL-6 and IL-10 production and DNA synthesis in peripheral blood mononuclear cells. Horm Metab Res. 1996;28(6):267–270. doi: https://doi.org/10.1055/s-2007-979789Reinhold D, Ansorge S, Schleicher ED. Elevated glucose levels stimulate transforming growth factor-beta 1 (TGF-beta 1), suppress interleukin IL-2, IL-6 and IL-10 production and DNA synthesis in peripheral blood mononuclear cells. Horm Metab Res. 1996;28(6):267–270. doi: https://doi.org/ 10.1055/s-2007-979789.Richard C, Wadowski M, Goruk S, et al. Individuals with obesity and type 2 diabetes have additional immune dysfunction compared with obese individuals who are metabolically healthy. BMJ Open Diabetes Res. Care. 2017;5(1):e000379Richard C, Wadowski M, Goruk S, et al. Individuals with obesity and type 2 diabetes have additional immune dysfunction compared with obese individuals who are metabolically healthy. BMJ Open Diabetes Res. Care. 2017;5(1):e000379.Petersen MC, Shulman GI. Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018;98(4):2133–2223. doi: https://doi.org/10.1152/physrev.00063.2017Petersen MC, Shulman GI. Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018;98(4):2133–2223. doi: https://doi.org/10.1152/physrev.00063.2017Manolios N, Papaemmanouil J, Adams DJ. The role of ion channels in T cell function and disease. Front Immunol. 2023;14:1238171. doi: https://doi.org/10.3389/fimmu.2023.1238171. eCollection 2023Manolios N, Papaemmanouil J, Adams DJ. The role of ion channels in T cell function and disease. Front Immunol. 2023;14:1238171. doi: https://doi.org/10.3389/fimmu.2023.1238171. eCollection 2023.Chen J, Li L, Li Y, et al. Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling through connexin43- mediated Ca2+ influx. Cardiovasc. Diabetol. 2015;14:22. doi: https://doi.org/10.1186/s12933-015-0183-6Chen J, Li L, Li Y, et al. Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling through connexin43-mediated Ca2+ influx. Cardiovasc. Diabetol. 2015;14:22. doi: https://doi.org/ 10.1186/s12933-015-0183-6.Sun F, Xiong S and Zhu Z. Dietary capsaicin protects cardiometabolic organs from dysfunction. Nutrients. 2016; 8(5):174. doi: https://doi.org/10.3390/nu8050174Sun F, Xiong S and Zhu Z. Dietary capsaicin protects cardiometabolic organs from dysfunction. Nutrients. 2016; 8(5): 174. doi: https://doi.org/ 10.3390/nu8050174Wang P, Yan Z, Zhong J, et al. Transient receptor potential vanilloid 1 activation enhances gut glucagon-like peptide-1 secretion and improves glucose homeostasis. Diabetes. 2012;61(8):2155–2165. doi: https://doi.org/10.2337/db11-1503Wang P, Yan Z, Zhong J, et al. Transient receptor potential vanilloid 1 activation enhances gut glucagon-like peptide-1 secretion and improves glucose homeostasis. Diabetes. 2012;61(8):2155–2165. doi: https://doi.org/ 10.2337/db11-1503Kang JH, Kim CS, Han IS, et al. Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissues and isolated adipocytes, and suppresses the inflammatory responses of adipose tissue macrophages. FEBS Lett. 2007;581(23):4389–4396. doi: https://doi.org/10.1016/j.febslet.2007.07.082Kang JH, Kim CS, Han IS, et al. Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissues and isolated adipocytes, and suppresses the inflammatory responses of adipose tissue macrophages. FEBS Lett. 2007; 581(23):4389–4396. doi: https://doi.org/ 10.1016/j.febslet.2007.07.082.Khalil M, Alliger K, Weidinger C, Yerinde C, Wirtz S, Becker C, Engel MA. Functional Role of Transient Receptor Potential Channels in Immune Cells and Epithelia. Frontiers in Immunology. 2018;9:174. doi: https://doi.org/10.3389/fimmu.2018.00174Khalil M, Alliger K, Weidinger C, Yerinde C, Wirtz S, Becker C, Engel MA. Functional Role of Transient Receptor Potential Channels in Immune Cells and Epithelia. Frontiers in Immunology. 2018;9:174. doi: https://doi.org/10.3389/fimmu.2018.00174.

The authors declare that there are no conflicts of interest present.