高脂饲料诱导的大鼠胰岛素抵抗及其与血清瘦素的关系

High fat diet-induced insulin resistance and its relationship with serum leptin in the rat

摄入大量脂肪被认为是胰岛素抵抗 (insulinresistance ,IR)形成的一个主要因素 ,本工作根据StorlienLH的配方制作高脂饲料 ,分别喂饲成年雄性SD大鼠 30d和 或 6 0d ,用KraegenEW方法建立正糖钳技术评估IR ,观察IR形成和发展过程中基础血清瘦素和胰岛素刺激下血清瘦素的变化。结果喂饲大鼠高脂饲料 30d形成IR ,其血糖 ,血清瘦素水平 ,肩胛区脂肪、肾周脂肪、附睾脂肪垫重量均较对照组显著升高 (均P <0 0 1) ,但血清胰岛素水平与对照组比较无差别 ;喂饲大鼠高脂伺料 6 0d ,IR程度和高血糖水平与 30d高脂组仍一样 ,血清瘦素水平和三处脂肪重量进一步升高 (P <0 0 0 1和 0 0 1) ,出现高胰岛素血症 (P <0 0 5 ) ;但喂饲高脂 30和 6 0天动物体重增长和正糖钳实验中灌流胰岛素 2h后的血清瘦素水平与对照组无差别。结果提示高脂饲料可诱导正常成年大鼠形成IR ,体脂增高 ,高血糖 ,高瘦素血症是这类IR大鼠的特征 ,而高瘦素血症可能是IR形成的原因 。

The present studies were designed to ① establish a rat model of IR by feeding the rat either a high fat diet or a lab chow for 30 days and 60 days respectively. ② perform euglycemic hyperinsulinemic clamp technique, to study insulin action in vivo after feeding. ③ measure basal blood glucose, serum insulin, serum leptin before and after feeding, and serum leptin after clamp study. ④ weigh body weight after 10days feeding ,and body fat(epididymal, perirenal, interscapular) after clamp study. The results showed that HiFAT fed rats accumulated significantly more fat despite the same rate of overall weight gain. A significant increase in basal blood glucose was evident in rats fed with HiFAT diet 30 days and this trend continued throughout the dietary protocol. Basal serum insulin was increased only in the rat fed with HiFAT diet 60 days. Clamp studies showed that HiFAT animals displayed IR after 30 days of feeding, which persisted after 60 days of treatment. The increase of basal serum leptin was seen in all dietary groups and was correlated with body weight gain. However basal serum leptin was significantly elevated in HiFAT rat compared with control rat, and in rat fed the fat-rich diet for 60 days compared with for 30 days. Insulin-stimulated serum leptin did not differ significantly among experimental treatment groups. This study indicated that feeding healthy rats a high fat diet resulted in IR. The increase of fat storage , basal blood glucose and serum leptin is character of IR rat induced by high fat diet. Basal hyperleptinaemia rather than basal hyperinsulinaemia may be a cause of IR.