Obesity is pathology associated with chronic low-grade inflammation, which is characterized by infiltration of adipose tissue with activated macrophages. Resident macrophages are able to produce cytokines which are key molecules in the onset of insulin resistance and, consequently, type 2 diabetes. Whereas, adipokine such as adiponectin produced by the white adipose tissue, reduce systemic insulin resistance. Osteopontin (OPN) is a cytokine expressed in the site of inflammation known to be strongly upregulated in obese adipose tissue, in contrast to adiponectin, which is well known to be downregulated by obesity. Recent works point towards a critical role of local macrophage proliferation in adipose tissue inflammation and my own data suggest that in obesity viability of macrophages is enhanced and apoptosis diminished. Inflamed adipose tissue is also key player in liver pathologies connected with fat accumulation and fibrosis. These processes involve glycerol uptake in liver with channel proteins such as aquaporins (AQPs) facilitating the transport of the latter through the cell membrane. Therefore, I hypothesised that OPN may contribute to local macrophage proliferation. Moreover, adipokines might influence AQPs function and hepatic stellate cells activation. In this thesis I aimed at investigating effects of obesity-induced alterations of cytokine production by determining OPN effects on monocyte and macrophage proliferation and their relevance in the context of adipose tissue inflammation. As a second approach, liver AQPs expression and function was studied in relation to the obesity-induced decrease of adiponectin production. Survival of human monocytes was enhanced by OPN, while apoptosis was diminished. Proliferation rates in human and mice monocytes/macrophage increased by OPN in parallel. In liver, serum adiponectin correlated with AQPs gene expression in human. Moreover, AQP3 expression was strongly induced by adiponectin, increasing lipid content and glycerol uptake in hepatic stellate cells (HSC).
In conclusion, OPN increases macrophage abundance in obese adipose tissue also by inhibiting apoptosis and enhancing their local proliferation. Second, adiponectin may counteract the progress of fatty liver disease to fibrosis by leading HSC into a quiescent functional state. Hence in this thesis, I could demonstrate novel effects of important adipokines with potential impact on the prognosis of obese patients.