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概况有关。我们利用自己开发的CT扫描技术提出了一种新的肥胖人体测量学分类，一种是“内脏脂肪肥胖”，其特征是脂肪在腹腔内明显堆积，另一种是“皮下脂肪肥胖”，脂肪堆积主要集中在皮下区域。内脏脂肪型肥胖的糖脂代谢紊乱比皮下脂肪型肥胖更为显著。在本研究中，我们探讨了内脏脂肪性肥胖的发病机制和病理生理。研究了内脏脂肪型肥胖患者减重后脂肪分布的变化。体重减轻后，内脏脂肪比身体其他部位的脂肪减少更多，代谢异常改善的程度与体重减轻后内脏脂肪减少的程度相关。在体重正常的2型糖尿病或高脂血症患者中也观察到主要的腹腔脂肪堆积。vmh损伤大鼠的动物实验显示，肠系膜脂肪堆积程度与高血糖和高甘油三酯血症程度密切相关。门静脉游离脂肪酸（FFA）随肠系膜脂肪含量的增加而升高。过多的FFA流入肝脏可能导致脂蛋白的过量产生，也可能导致胰岛素敏感性降低和葡萄糖代谢紊乱。作为引起内脏脂肪堆积的因素，高糖饮食促进了vmh损伤的肥胖大鼠肠系膜脂肪堆积。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性，从而在脂肪组织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.