Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Leuven, Belgium.
Thromb Res. 2011 Feb;127 Suppl 3:S17-20. doi: 10.1016/S0049-3848(11)70006-8.
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.
肥胖是一种常见的疾病，与之相关的疾病，如糖尿病、动脉粥样硬化、高血压、心血管疾病和癌症，是西方社会死亡率和发病率的主要原因。肥胖的发展与脂肪组织的广泛改变有关，包括脂肪生成、血管生成和细胞外基质蛋白水解。纤溶（纤溶酶原/纤溶酶）和基质金属蛋白酶（MMP）系统在这些过程中协同作用。脂肪生成与血管生成密切相关，这一点可以从以下发现中看出：脂肪组织外植体触发血管形成，而反过来脂肪组织内皮细胞促进前脂肪细胞分化。在转基因小鼠中，营养诱导的肥胖模型已被广泛用于研究纤溶和 MMP 系统以及血管生成在肥胖发展中的作用。大多数研究支持这些系统在脂肪生成和肥胖中的作用，并表明它们的调节可能会影响脂肪组织的发育。这些模型还表明，用雌激素治疗肥胖雌性小鼠可通过降低脂肪生成基因的表达，有改善肥胖、胰岛素抵抗和葡萄糖不耐受的潜力。因此，肥胖的啮齿动物模型是研究脂肪组织发育机制以及激素治疗效果的非常有用的工具。
