Dr. Iryna Kompanets

Taras Shevchenko National University of Kyiv

Presentation title: "Biomedical research in Taras Shevchenko National University of Kyiv (Ukraine): the role of immune cells in obesity"

Abstract: Inflammation is thought to be the hallmark of obesity. The production of adipokines and chemokines by adipocytes causes macrophage recruitment to the adipose tissue resulting in low-grade local inflammation and permanent oxidative stress. The aggravation of inflammatory conditions leads to proinflammatory cytokine production by blood monocytes and the establishment of the inflammatory state in distant organs and tissues. Substantial progress in obesity study has been achieved on animal models of high-fat diet-induced obesity whereas the mechanism of progesterone-induced obesity remains incompletely clarified. Progesterone (Pg) is widely used for contraception and hormone replacement therapy. It enhances food intake and therefore causes significant weight gain by increasing fat deposition. The current study focused on clarifying the mechanisms of inflammatory response of immune cells in Pg-induced obesity and revealing the effects of yeast melanin and cerium dioxide nanoparticles as potential anti-obesity drugs.

In our studies, the female rats treated with Pg within 28 days demonstrated the rise of body weight up to 27% and elevation of body mass index by 2.3-times suggesting the development of obesity. We have shown the stimulation polarization of peritoneal macrophages towards the M1 pro-inflammatory type (enhanced NO-production) and suppression of their M2 polarization (decreased arginase activity). It was associated with the increase of pro-inflammatory cytokine IL-1 and IFN-γ levels and the decrease of IL-4, IL-10, and TGF-β anti-inflammatory cytokine levels in the blood serum of Pg-treated rats. The serum level of medium size circulative immune complexes was elevated suggesting the aggravation of the inflammatory process. These results reflect the development of systemic inflammatory response in Pg-induced obesity and are consistent with the reported data from murine high-fat diet models.

Antioxidants have attracted particular attention as a promising tool for oxidative stress alleviation and therefore could be prospective drugs in obesity treatment. In the current study, we focused on melanin from Antarctic black yeast Nadsoniella nigra and established its anti-obesity and anti-inflammatory effects on an animal model of Pg-induced obesity. Melanin prevented the weight gain and the fat mass growth caused by progesterone. It also suppressed the M1 polarization of peritoneal macrophages decreasing NO production and ROS level in peritoneal macrophages and decreasing the circulative immune complexes level. Melanin possesses the same effects when it is used simultaneously with Pg (prophylaxis model) and one month after Pg treatment (cure model).

Cerium dioxide nanoparticles (CeO₂NPs) are promising potential therapeutics due to their ability to destroy reactive oxygen species and to very low toxicity. They may be useful for preventing or ameliorating oxidative stress-related pathologies, cancer diseases, and aging. These nanoparticles may have the potential to alleviate the negative effects of obesity - the disease associated with long-term oxidative stress and inflammation. Our data from the rat model of Pg-induced obesity indicate that cerium dioxide nanoparticles prevent weight gain in rats and potently suppress the M1 polarization of peritoneal macrophages decreasing the NO-production.

Taken together, our results show that systemic inflammatory response in Pg-induced obesity involves the resident lymphocytes of peritoneal cavity and is suppressed by antioxidant compounds yeast melanin and cerium dioxide nanoparticles. Despite the available data, further studies are needed to deeply understand the mechanisms of inflammatory response in obesity of different origins and to clarify the role of antioxidants in its treatment and prevention.