SIRT1 CONTRIBUTES TO POLARIZATION OF PERIPHERAL BLOOD MONOCYTES BY INCREASING STAT6 EXPRESSION IN YOUNG PEOPLE WITH OVERWEIGHT AND LOW-RISK OBESITY.

Obesity contributes to the formation of low-intensity systemic inflammation with major participation of monocytes/macrophages. Nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase class III SIRT1 regulates the polarization of macrophages, controlling the inhibition of the M1 subpopulation and stimulating the activation of M2 macrophages. The aim of our study was to determine the regulatory role of SIRT1 in M1/M2 polarization of peripheral blood monocytes in young people with overweight and Class I obesity. 30 subjects of both gender, aged 18-25 years have been examined. Groups were formed by the BMI: the subjects with normal body weight (n=10, BMI 18.50-24.99 kg/m2), the subjects with overweight (n=10, BMI 25.00-29.99 kg/m2), the subjects with Class I obesity (n=10, BMI 30.00-34.99 kg/m2). Peripheral blood mononuclear suspension was isolated from venous blood. E. coli lipopolysaccharide (LPS) at a dose of 100 ηg/mL and γ-interferon (γIFN) at a dose of 100 ηg/mL were used to induce polarization of macrophages by the M1 phenotype. Unstimulated monocytes/macrophages were used as controls. The level of the stat1, stat6 and sirt1 gene expression was determined by Polymerase Chain Reaction Real-time PCR. The findings showed an increase in the level of the sirt1 gene expression with weight gain. The highest rates of sirt1 expression were found in IL-4-stimulated cells of the subjects with Class I obesity. It has been concluded that SIRT1 promotes M2 polarization of peripheral blood monocytes toward the anti-inflammatory phenotype in young people with overweight and Class I obesity, mediated by increased stat6 gene expression. The direction of polarization toward the anti-inflammatory phenotype is indicated by a decrease in the stat/stat6 ratio and the formation of correlation between the sirt1 and stat6 expression in LPS and γIFN-stimulated cells and IL-4-stimulated cells.