Abstract
Overweight and obesity lead to the formation of a pro-inflammatory phenotype of the adipose tissue macrophages, but it is not known how exactly the balance of STAT1 and STAT6 transcription factors is implemented in the peripheral blood monocytes and how this affects the further polarization process in overweight. The article examines the level and ratio of expression of the STAT1 and STAT6 transcription factors in the polarization of the peripheral blood monocytes depending on the body weight. The study enrolled 20 women and men aged from 18 to 25 years. In terms of BMI, the subjects were divided into the following groups: individuals with normal body weight (BMI 18.50-24.99 kg/m2), represented by 5 women and 5 men; overweight individuals (BMI 25.00-29.99 kg/m2), including 5 men and 5 women. Using standard methods peripheral blood monocytes stimulated by LPS and γIFN, IL-4 was isolated and incubated for 3 and 7 days. PCR method was used to determine the expression level of the stat1 and stat6 genes in incubated cells. The concentration of IL-6 and TGFβ1 was measured in the supernatant on the 7th day of incubation, and TGFβ1 and hs-CRP in the serum of the subjects. The obtained results revealed a significant increase in the level of IL-6 in the supernatant of macrophages stimulated by LPS and γIFN in overweight individuals. The level of hs-CRP in the serum was also significantly higher in overweight individuals. It has been shown that under the conditions of overweight development, there is a significant increase in the level of expression of stat1 and stat6 genes in cells stimulated by IL-4. The obtained data indicate the presence of a preconditioning state of the peripheral blood monocytes with activation of signaling networks mainly in macrophages stimulated by the M2 phenotype under conditions of increased nutrients intake.
Highlights
Excessive accumulation of metabolically active adipose tissue in overweight and obesity leads to chronic systemic inflammation of low intensity and significant infiltration of the tissue by macrophages [1].Cells of the monocyte-macrophage line are characterized by significant diversity, plasticity, and flexibility, which are the key features of mononuclear phagocytes and states of their activation [2, 3]
The obtained findings showed that in individuals with normal body weight, the expression level of stat1 was significantly higher in macrophages stimulated by LPS and γIFN, IL-4 as compared to unstimulated cells on the 3rd day of incubation
The expression of stat1 in macrophages stimulated by IL-4 is significantly higher as opposed to macrophages stimulated by LPS and γIFN (Table 1)
Summary
Excessive accumulation of metabolically active adipose tissue in overweight and obesity leads to chronic systemic inflammation of low intensity and significant infiltration of the tissue by macrophages [1]. Cells of the monocyte-macrophage line are characterized by significant diversity, plasticity, and flexibility, which are the key features of mononuclear phagocytes and states of their activation [2, 3]. During the development of overweight and obesity, the number of macrophages of the M1 subpopulation increases and correlates with inflammation in the adipose tissue, which contributes to further weight gain and possible insulin resistance. M1 macrophages produce pro-inflammatory cytokines and induce aerobic glycolysis. In individuals with normal body weight, macrophages of the M2 subpopulation predominate; they secrete anti-inflammatory cytokines and use oxidative metabolism to maintain homeostasis [4]
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