脂肪細胞における肥満遺伝子とインスリン作用関連遺伝子の制御機構の研究

(1)噻唑烷二酮类药物对大鼠脂肪细胞瘦素生成及胰岛素作用的影响。胰岛素增敏剂噻唑烷二酮在24小时后降低了大鼠脂肪细胞中瘦素的蛋白和mRNA水平。该化合物还增加了脂肪细胞对2-脱氧葡萄糖的摄取。而外源性瘦素对脂肪细胞孵育24小时后，瘦素mRNA水平和胰岛素作用均无明显影响，提示外源性瘦素剂量对脂肪细胞原代培养无直接影响。(2)瘦素对培养的骨骼肌（L6细胞）胰岛素作用的影响，包括胰岛素信号系统和葡萄糖摄取。(3)瘦素转基因小鼠的胰岛素作用瘦素转基因小鼠没有脂肪细胞的积累，无论是白色脂肪细胞还是棕色脂肪细胞。通过腹腔葡萄糖耐量试验（GTT）和胰岛素耐量试验（ITT）测定的体内胰岛素作用显示转基因小鼠的胰岛素敏感性增强。提示瘦素对脂肪细胞和胰岛素的作用有脂肪萎缩作用，并且瘦素通过中枢神经系统增强胰岛素的作用。(4)人血浆瘦素浓度与% fat、体质指数呈显著相关。瘦素浓度也存在性别差异（男性<女性）。然而，老化对浓度没有影响。在日本肥胖人群中，我们也发现了一些瘦素基因的多态性，但与瘦素基因的多态性没有关系。

(1) Effect of thiazolidinediones on leptin production and insulin action in rat adipocytes. Thiazolidinedione, an insulin sensitizer, reduced protein and mRNA levels of leptin in rat adipocytes after 24 hours. This compound also increased 2-deoxyglucose uptake in the adipocytes. However, mRNA level of leptin and insulin action were not changed, when the adipocytes were incubated with exogenous leptin for 24 hours, Thus it is suggested that exogenous leptin dose not affect the primary culture of adipocytes directly.(2) Effect of leptin on insulin action in culture of skeletal muscle Leptin did not affect the insulin action including insulinsignaling systems and glucose uptake in culture of skeletal muscles (L6 cells).(3) Insulin action in leptin transgenic mouse Leptin transgenic mouse showed no accumulation of adipocytes, both white and brown adipocytes. In vivo insulin action determined by intraperitoneal glucose tolerance test (GTT) and insulin tolerance test (ITT) showed enhanced insulin sensitivity in the transgenic mice. It is suggested that leptin has lipoatrophic effect on adipocytes and insulin action, and that insulin action is enhanced Through central nervous systems by leptin.(4) Concentration of plasma leptin in human There were correlations between plasma leptin and % fat , body mass index significantly. And the was also gender difference in leptin concentration (male<female). However aging did not affect the concentration. We also found some polymorphisms in leptin gene, but there were no relation between leptin and the polymorphisms in Japanese obese subjects.