Obesity is a common disorder, and related diseases such as diabetes,
atherosclerosis,
hypertension,
cardiovascular disease and
cancer are a major cause of mortality and morbidity in Westerntype societies. Development of
obesity is associated with extensive modifications in adipose tissue involving adipogenesis, angiogenesis and extracellular matrix proteolysis. The fibrinolytic (
plasminogen/
plasmin) and
matrix metalloproteinase (
MMP) systems cooperate in these processes. Adipogenesis is tightly associated with angiogenesis, as shown by the findings that adipose tissue expiants trigger blood vessel formation, whereas in turn adipose tissue endothelial cells promote preadipocyte differentiation. A nutritionally induced
obesity model in transgenic mice has been used extensively to study the role of the fibrinolytic and
MMP systems and of angiogenesis in the development of
obesity. Most studies support a role of these systems in adipogenesis and
obesity, and suggest that their modulation may affect development of adipose tissue. Such models have also shown that treatment of obese female mice with
estrogens has the potential to improve
obesity,
insulin resistance and
glucose intolerance, via decreased expression of lipogenic genes. Thus, murine models of
obesity have been very useful tools to study mechanisms of adipose tissue development, as well as effects of hormonal
therapy.