AP19575254 «The effect of melatonin on the phenotypic and functional characteristics of myeloid suppressor cells in a model of obesity combined with circadian rhythm disorder.»

Relevance

 It is known that disruption of circadian rhythms leads to the development of inflammatory reactions and impairs immune functions, and is also a risk factor for the development and/or progression of various diseases, including obesity. Obesity as a disease has now become a widespread and serious public health problem throughout the world. Obesity has been shown to increase the risk of certain diseases such as type 2 diabetes, cancer, etc. and lead to decreased quality of life. Obesity is characterized not only by weight gain and excess accumulation of adipose tissue, but also by a chronic inflammatory process caused by the release of inflammatory adipokines from adipose tissue, immune cells and molecular mediators of inflammation. Recently, myeloid-derived suppressor cells (MDSCs) have been demonstrated to be one of the most important promoters of chronic inflammation. The level of these cells is significantly increased in circadian rhythm disorders and obesity. Disruption of circadian rhythms leads to dysregulation of melatonin secretion, which can regulate the functions of various cells of the adaptive and innate immune system, the differentiation of cells in the bone marrow and their accumulation in the periphery, and the production of inflammatory cytokines. We hypothesized that melatonin may also be involved in modulating the differentiation and activity of MDSC. Therefore, this study aimed to investigate the effect of melatonin on myeloid suppressor cells in a model of circadian disturbances combined with obesity.

 Target:

The aim of the project is to evaluate the effect of melatonin on the induction of MDSCs, as well as on their phenotypic and functional characteristics in experimental obesity in combination with circadian rhythm disturbances. This opens the way to understanding the immunoregulatory mechanisms underlying the pathological processes that develop against the background of obesity and circadian rhythm disturbances.

 Expected results:

 During the implementation of the project work, it is expected to prove the following questions: 1) disruption of the circadian rhythm affects the immune response and prolongs the inflammatory process in obesity, promoting the accumulation of MDSC; 2) the circadian rhythm regulator melatonin inhibits MDSC functions and/or enhances the immune response. The results obtained will help identify the causes and mechanisms of immune disorders associated with obesity and circadian disorders. Thus, the study results may provide necessary information for the effective treatment of chronic diseases associated with circadian rhythm disturbances and obesity. This, in turn, will allow us to find effective ways to combat chronic diseases.

 National and international significance of the project:

 A clear epidemiological connection has been established between circadian disturbances and the pathogenesis of obesity. Obesity is a common and global problem that increases the risk of complications and death from other chronic diseases, including diabetes, heart disease and some types of cancer. This reduces the quality and life expectancy of people. Exacerbates national and global health and economic problems. Therefore, studying the phenotypic and functional changes in myeloid suppressor cells during the development of obesity in combination with circadian disorders and determining the effect of melatonin on the accumulation and functional specificity of MDSC will help to understand the cause and mechanisms of immune disorders in associated diseases. circadian disorders. In turn, this makes it possible to create effective ways to combat and treat chronic diseases both in Kazakhstan and abroad.

Information for potential users:

 According to WHO estimates, overweight and obesity are the fifth leading cause of death in the world. More than 2 billion people in the world live with the pathology of obesity. In addition, at least 2.8 million adults die each year due to overweight or obesity, and this number continues to rise. In addition, due to overweight and obesity, other pathologies develop, including 44% diabetes mellitus, 23% coronary heart disease, 7% — 41% some cancers. An increase in obesity was also observed in Kazakhstan. The Kazakh Academy of Nutrition reported that over the past 20 years, the prevalence of overweight and obesity among children under 5 years of age has increased from 9% to 13.4%. This study is important for determining the cellular mechanisms of regulation of the immune response in the dynamics of the development of obesity associated with experimental circadian disorder. The results obtained during the implementation of this Project will contribute to the understanding of the processes involved in the immune pathogenesis of not only metabolic disorders or obesity, but also other chronic diseases that develop with them, as well as scientific progress in the field of prevention and treatment of these diseases.

Area of application: cellular and molecular immunology. Immunological mechanism of chronic inflammation

 Research group:

 Abdollah N. — PhD (biology), project supervisor, acting head of the laboratory. H-index: 6. ORCID: https://orcid.org/0000-0002-4769-7824. Scopus ID: 57194001982. Web of Science ID: R-2193-2016.

Perfileva Yu.V. — PhD (biology), leading researcher. H-index: 7. ORCID: https://orcid.org/0000-0001-6803-0773. Scopus ID: 56823500600. Web of Science ID: AAF-9666-2020.

Ostapchuk E.O. – PhD (biology), leading researcher. H-index: 9. ORCID: https://orcid.org/0000-0002-3771-423X. Scopus ID: 56823472400. Web of Science ID: D-1254-2015.

Narmuratova G.Kh. – PhD-doctoral student (biomedine) of the Biology Faculty of al-Farabi Kazakh National University.

Aben D. — MSc

Abdusattarova Yu. – MSc