JAK/STAT SIGNALING: NEW PERSPECTIVES IN THE DIAGNOSIS OF OBESITY



Cite item

Full Text

Abstract

Abstract

The problem of obesity has not tended to be resolved over the past decades. It has been proven that obesity is one of the important pathogenetic factors of metabolic disorders in the body, leading to the development of various pathologies. Despite numerous studies, the results of which clarify aspects of the pathogenesis of obesity and associated changes in metabolism, many questions remain. The aim of this study was to study the components of the JAK / STAT signaling system - proteins STAT1, STAT3, SOCS1, SOCS3, as well as the level of cytokine IL-6 in the blood serum of obese individuals. 210 patients were examined, divided into groups: I - individuals with normal body weight; II - patients with overweight; III - patients with metabolically healthy obesity, IV - patients with metabolically unhealthy obesity. A set of immunological and general clinical research methods was used in the work. The study revealed significantly altered values of JAK/STAT signaling system components and IL-6 cytokine levels in the blood serum in obese patients. Increased IL-6 cytokine levels in the blood serum were found in obese patients, as well as statistically significant correlation of IL-6 with lipid profile parameters, STAT1,3 and SOCS1,3 proteins. STAT1 and STAT3 levels were decreased in obese individuals in contrast to individuals with normal and overweight body weight. An imbalance of SOCS1 and SOCS 3 proteins was also observed in individuals with different obesity phenotypes. Significant correlations were established between serum IL-6, STAT1, STAT3, SOCS1 and SOCS3 levels and lipid metabolism parameters in patients with MHO and MUO. The results of the conducted studies are consistent with the available literature data on changes in the expression of STAT1,3 and SOCS1,3 proteins in obese patients, the importance of SOCS1,3 proteins in the regulation of STAT expression by the principle of negative feedback, the participation of the cytokine IL-6 in the activation of the JAK/STAT signaling system and the maintenance of meta-inflammation in obese individuals. Thus, the study of JAK/STAT signaling indicators may be a promising direction in diagnostics and the search for new strategies in the fight against obesity.

About the authors

Anastasiia Kulakova

"Oryol State University named after I.S. Turgenev", Oryol, Russian Federation;
LLC «Medical center «My doctor» Bryansk, Russia

Author for correspondence.
Email: Kulakovaas@mail.ru
ORCID iD: 0000-0002-5828-8620

research fellow at the laboratory of molecular, translational and digital cardioimmunology at the "Oryol State University named after I.S. Turgenev"; gastroenterologist, therapist, nutritionist

Russian Federation, LLC «Medical center «My doctor»,241019, Bryansk, Russia, Krasnoarmeyskaya St., 100

References

  1. [Volkova N.I., Ganenko L.A., Porksheyan M.I. Metabolically healthy obesity, what do we know about it? Medical Bulletin of the South of Russia, 2017. Vol. 8. No. 3. pp. 6-16. (In Russ.)]
  2. [Kulakova A.S., Snimshchikova I.A., Plotnikova M.O. Features of the state of the STAT-signaling system in obese patients//Medical Bulletin of Bashkortostan.2020. Vol. 15. No. 2. pp.22-25. (In Russ.)]
  3. Abiri B., Hosseinpanah F., Banihashem S., Madinehzad S., Valizadeh M. Mental health and quality of life in different obesity phenotypes: a systematic review , 2022, Vol. 20, pp. 63. doi: 10.1186/s12955-022-01974-2
  4. Grohmann M., Wiede F., Dodd G. Obesity Drives STAT-1-Dependent NASH and STAT-3-Dependent HCC, 2018, Vol.175, no. 5, pp. 1289–1306.e20. doi: 10.1016/j.cell.2018.09.053
  5. Kolb R., Sutterwala F., Zhang W. Obesity and cancer: inflammation bridges the two. Curr Opin Pharmacol, 2016, Vol. 29, pp.77-89. doi: 10.1016/j.coph.2016.07.005. Epub 2016 Jul 16.
  6. Lopez-Jimenez F., Almahmeed W., Bays H. Obesity and cardiovascular disease: mechanistic insights and management strategies. A joint position paper by the World Heart Federation and World Obesity Federation.European Journal of Preventive Cardiology, 2022. Vol. 29, no. 17, pp. 2218–2237. doi: https://doi.org/10.1093/eurjpc/zwac187
  7. Pessentheiner A., Ducasa G., Gordts P. Proteoglycans in Obesity-Associated Metabolic Dysfunction and Meta-Inflammation. Front Immunol, 2020, Vol. 11, pp. 769. doi: 10.3389 /fimmu.2020.00769
  8. Preda A., Carbone F., Tirandi A., Montecucco F., Liberale L. Obesity phenotypes and cardiovascular risk: From pathophysiology to clinical management. Rev Endocr Metab Disord, 2023, Vol. 24, no. 5, pp. 901-919. doi: 10.1007/s11154-023-09813-5. Epub 2023 Jun 26.
  9. Richard A., Stephens J. The role of JAK-STAT signaling in adipose tissue function. Biochim Biophys Acta, 2014, Vol. 1842, no.3, pp. 431–439. doi: 10.1016/j.bbadis.2013.05.030
  10. Russo S, Kwiatkowski M, Govorukhina N, Bischoff R, Melgert B. Meta-Inflammation and Metabolic Reprogramming of Macrophages in Diabetes and Obesity: The Importance of Metabolites. Front Immunol, 2021, Vol. 12, pp. 746151. doi: 10.3389/fimmu.2021.746151. eCollection 2021
  11. Wunderlich C., Hövelmeyer N., Wunderlich F. Mechanisms of chronic JAK-STAT3-SOCS3 signaling in obesity. JAKSTAT, 2013, Vol.2, no 2. e23878. doi: 10.4161/jkst.23878
  12. Xu D., Yin C., Wang S., Xiao JAK-STAT in lipid metabolism of adipocytes. JAKSTAT, 2013, Vol.2, no 4. e27203. doi: 10.4161/jkst.27203
  13. Yang M., Tian M., Zhang X. Role of the JAK2/STAT3 signaling pathway in the pathogenesis of type 2 diabetes mellitus with macrovascular complications.Oncotarget.2017,Vol.8.pp.96958- 96969. doi: https://doi.org/10.18632/oncotarget.18555

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) Kulakova A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № 77 - 11525 от 04.01.2002.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies