Collagen XVIII in adipose tissues and lipid metabolism

The aim of this PhD thesis was to increase the understanding of an extracellular matrix (ECM) component collagen XVIII as a regulator of adipose tissue (AT) expansion and functions. AT stores lipids and secretes number of signaling molecules and functions as an important regulator of glucose and lipid metabolism. Excess or scarcity of fat tissues predisposes to the metabolic dysfunctions, such as type 2 diabetes. The ECM gives structural support for the cells and acts as an important regulator of cellular behavior. This PhD study shows that collagen XVIII-deficient mice fed with a high fat diet develop lipodystrophia, a condition of ectopic lipid accumulation in the liver and circulation. Additionally, a novel role for collagen XVIII as a regulator of energy metabolism in the brown AT was identified in this study. Inactivation of Col18a1 gene led to increased heat production at low temperatures and restored the abnormally high blood triglyceride levels of collagen XVIII-deficient mice to normal level due to increased activity of the brown AT. We showed that collagen XVIII knockout mice have more adipose progenitor cells in white ATs as the control mice. This observation was studied further using the gold standard in vitro adipocyte differentiation models employing isolated mouse embryonic stem cells and subcutaneous stromal vascular fraction cells. These models did not reveal differences in the adipogenic capacity between the control and collagen XVIII deficient cells, which may indicate the inability of these models to accurately recapitulate the complex process of in vivo adipogenesis. The results presented in this PhD thesis highlight the importance of a single ECM protein, collagen XVIII, in various ATs and in the regulation of lipid storage. The findings presented in this PhD thesis contribute to a better understanding of basic mechanisms of AT development and functions which is also crucial for the development of new therapeutic strategies against obesity and metabolic disorders.