Role of immune and adipose cells in the development of adipose tissue inflammation induced by stress associated with obesity

1 SUMMARY Obesity and overfeeding are associated not only with increased circulating levels of nutrients and metabolites, but also with increased risk of the development of additional disorders, such as cardiovascular diseases, cancer or insulin resistance. Plausible link between obesity and its comorbidities is inflammatory state, observed on the whole body level as well as in AT. As possible initiators of this inflammation, hypertrophied adipocytes were suggested. Adipocytes per se secrete a spectrum of heterogeneous molecules including cytokines. Under the stress conditions, adipocytes and subsequently AT resident immune cells switch to pro-inflammatory state and via secretory signaling attract additional immune cells. Furthermore, hypertrophic adipocytes release higher levels of metabolites that may also contribute to pro- inflammatory polarization of immune cells, mainly macrophages. General aim of this thesis was to investigate connection between impaired levels of nutrients and pro-inflammatory statue and activation of immune cells in healthy (obese and lean) subjects. In the Part one of this thesis, we analyzed acute reaction of immune cells in circulation and AT on artificially elevated levels of nutrients, imitating its increased values typical for metabolic syndrome. HFM ingestion led to..