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)噻唑烷二酮类对大鼠脂肪细胞产生瘦素及胰岛素作用的影响。噻唑烷二酮，胰岛素增敏剂，降低蛋白和瘦素在大鼠脂肪细胞的mRNA水平后24小时。该化合物还增加了脂肪细胞中的2-脱氧葡萄糖摄取。而外源性瘦素与脂肪细胞共同孵育24小时后，瘦素的mRNA水平和胰岛素的作用均无明显变化，提示外源性瘦素对脂肪细胞的原代培养无直接影响。(2)瘦素对体外培养的骨骼肌胰岛素作用的影响瘦素对体外培养的骨骼肌（L 6细胞）的胰岛素作用（包括胰岛素信号系统和葡萄糖摄取）无影响。(3)瘦素转基因小鼠中的胰岛素作用瘦素转基因小鼠显示没有脂肪细胞的积累，无论是白色还是棕色脂肪细胞。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有脂肪萎缩作用，对胰岛素作用也有影响，瘦素通过中枢神经系统增强胰岛素作用。(4)人血浆瘦素水平与%脂肪、体重指数呈显著相关。瘦素水平也存在性别差异（男<女）。然而，老化并不影响浓度。我们还发现了瘦素基因的一些多态性，但在日本肥胖者中瘦素与多态性之间没有关系。

(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.