Aleksandrov A. Biochemical and immunological parameters of rats under experimental model of progesterone-induced obesity.

The thesis is devoted to the study of biochemical and immunological parameters under the conditions of the development of progesterone-induced obesity and the potential effect of melanin on these processes. Despite substantial progress in obesity investigation the mechanism of progesterone-induced obesity remains obscured. It’s widely accepted that neuroactive steroid progesterone is the most fattening steroid hormone which can increase food intake. Today it is important to study the processes that involve in the course of obesity. Іt can help in the development of effective treatment. Progesterone oil solution in dose 10 mg/kg and melanin aqueous solution in dose 2 ml/kg from antarctic black yeast Nadsoniella nigra strain X1 were used in this paper. According to the obtained results, rats became obsessed under long-term progesterone administration. This is evidenced by increased indicators of body mass, body mass index, the amount of gonadal fat and feed intake. Moreover, analysis of the serum lipid and lipoprotein levels in rat under long-term progesterone administration showed significant disturbances in their metabolism. It was also determined that the serotonin metabolism system is involved in the development of progesterone-induced obesity in rats. There was detected a high level of pro-inflammatory cytokines (IL-1 and IFN-γ) and a low level of anti-inflammatory cytokines (IL-4, IL-10, TGF-β), which confirms the occurrence of systemic inflammation under progesterone-induced obesity. Based on the obtained results, we observed an increase in NO production and a decrease in the arginase activity of peritoneal macrophages of rats injected with progesterone, indicating their polarization by the proinflammatory M1 phenotype. Melanin administration prevents the development of obesity in rats under simultaneous administration of progesterone. The introduction of melanin led to normalization of body weight parameters, serotonin content in the brain, eliminating dyslipidemia, and also exhibiting anti-inflammatory properties through inhibition of inflammation by preventing peritoneal macrophages polarization by M1 type.