Studies on Pathogenesis and Pathophysiology of Visceral Fat Obesity, a New Criteria of Obesity based on fat Topography

与肥胖相关的代谢并发症的频率已被证明与身体脂肪分布的情况有关。我们利用自己开发的CT扫描技术提出了一种新的人体测量学肥胖分类方法，一种是以腹部脂肪显著积聚为特征的内脏脂肪肥胖，另一种是以皮下脂肪积聚为主要特征的皮下脂肪肥胖。内脏脂肪肥胖者糖脂代谢紊乱较皮下脂肪肥胖者更为明显。本研究对内脏脂肪肥胖症的发病机制和病理生理进行了研究，并对内脏脂肪肥胖症患者减肥后脂肪分布的变化进行了研究。减重后内脏脂肪的减少幅度最大，代谢异常改善的程度与减重后内脏脂肪的减少程度相关。在正常体重的2型糖尿病或高脂血症患者中，也观察到腹膜脂肪积聚。利用VMH损毁大鼠的动物实验表明，肠系膜脂肪积聚的程度与高血糖和高甘油三酯血症的程度密切相关。门静脉游离脂肪酸(FFA)也随肠系膜脂肪体积增加而升高。过量的FFA流入肝脏可能会导致脂蛋白的过度产生，还可能导致胰岛素敏感性降低和葡萄糖代谢紊乱。作为内脏脂肪蓄积的因素，高糖饮食促进了VMH模型肥胖大鼠的肠系膜脂肪蓄积。利用原代培养的前脂肪细胞进行的实验表明，肠系膜前脂肪细胞对复制和分化的刺激具有抵抗力，因此有可能在脂肪组织的发育过程中增加成熟脂肪细胞的细胞体积。

The frequency of metabolic complications associated with obesity has been shown to be related to the profile of body fat distribution. We have proposed a new anthropometric classification of obesity using CT scanning technique developed by us one is "visceral fat obesity" which is characterized by a marked fat accumulation in abdominal cavity and the other is "subcutaneous fat obesity" in which fat accumulations located mainly in subcutaneous area. The disturbance of glucose and lipid metabolism are more remarkable in visceral fat obesity than in subcutaneous fat obesity of obesity. In this study, we investigated pathogenesis and pathophysiology of visceral fat obesity.Changes of fat distribution after weight reduction were investigated in visceral fat obesity. After weight reduction, visceral fat decreased more than any other part of body fat, and the extent of improvement of metabolic aberrations correlted with the extent of decrease in viscreal fat after weight reduction. Predominant fat accumulation in the abdominal cavity were also observed in normal weight patients with type 2 diabetes or hyperlipidemia.Animal experiments using VMH-lesioned rats revealed that the extent of mesenteric fat accumulation is closely correlated to the extent of hyperglycemia and hypertriglyceridemia. Portal free fatty acid (FFA) were also higher in accordance with the volume of mesenteric fat. Excessive FFA flux into the liver may cause overproduction of lipoproteins and also might lead to reduction in insulin sensitivity and deranged glucose metabolism. As the factors which cause visceral fat accumulation, high sucrose diet promoted mesenteric fat accumulation in VMH-lesioned obese rats. Experiments using primary-cultured preadipocytes revealed that mesenteric preadipcytes were resistant to stimulation of replication and differentiation, consequently intending to increase cell volume of matured adipocytes at the development of adipose tissue.