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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.

The continuous rise of overweight and obesity is a major concern for present and future healthcare management. The aim of our study was to evaluate the influence of lifestyle changes on central regulatory mechanisms of maintaining energy homeostasis, insulin resistance and chronic systemic inflammation in 18-25 year old overweight patients. The anthropometric measurements were done for each patient, including body weight, height, waist circumference (WC), hip circumference (HC), waist to hip ratio, and body mass index (BMI). Patients were divided into two groups according to their BMI. 20 males and 21 females with BMI > 25 kg/m2 were included in the first, study, group. The second, control, group consisted of 16 males and 11 females with BMI - 18.5 - 24.9 kg/m 2. Lipid profile, fasting glucose and insulin levels, HOMA-IR, TNF-α, ceruloplasmin, neuropeptides Agouti-related protein - AgRP and kokain- and amphetamine-mediated transcript - CART were examined at the beginning of the study (Day 1) and after 10 week treatment period (Day 70). During the 10 week treatment period, people in the study group underwent physical exercise programs of 40-60 minute duration three times per week, and brisk walking during the remaining days. The mean calorie expenditure during the exercise was 500 kcal/day. Each patient in the study group was given balanced, healthy diet with 20% calorie restriction from baseline diet. Our study reveled that negative energy balance caused a statistically significant decrease in AgRP, reduction of visceral fat stores, increase of HDL, reduction of TNF-α and dissolution of insulin resistance signs. Significant but not statistically significant reduction of CART level was observed after increased physical activity program and calorie restriction diet, which might play an important role in the mechanism of decreasing weight. However, further investigations are required in order to determine its place in body weight regulation.