目的 通过普通饲料和高脂饲料喂养大鼠,探讨建立肥胖胰岛素抵抗大鼠模型的适宜条件和时间。方法 将45只6周龄雄性SD大鼠随机分为普通饲料对照组和高脂饲料组(脂肪供能比为45%), 喂养4周后剔除高脂饲料组肥胖抵抗(obesity resistance,OR)大鼠,肥胖(obese,OB)大鼠继续喂养至12周。分别于4、8、12周末进行口服葡萄糖耐量试验(oral glucose tolerance test,OGTT),12周末检测胰岛素释放、内脏脂肪、胰腺、肝脏等组织的病理变化。结果 高脂饲料喂养4周后,高脂饲料组大鼠的体质量比对照组高17.8%(P=0.001),肥胖成模率为67.6%~78.4%,OB大鼠出现糖耐量降低,OGTT 120 min血糖比对照组高27.5%(P<0.001),曲线下面积(area under the curve, AUC)比对照组高8.3%(P=0.037),79.3%的大鼠出现肥胖胰岛素抵抗;喂养8周时,OB大鼠体质量比对照组高30.4%(P<0.001),OGTT 60 min和120 min血糖分别比对照组高35.6%(P<0.001)和36.4%(P<0.001),AUC比对照组高21.7%(P<0.001),100.0%大鼠出现肥胖胰岛素抵抗;喂养12周时,OB大鼠体质量比对照组高36.9%(P<0.001),OGTT 60 min和120 min血糖分别比对照组高24.8%(P=0.001)和34.6%(P<0.001),AUC比对照组高16.1%(P=0.019),93.3%的大鼠出现肥胖胰岛素抵抗。胰岛素释放实验显示,高脂饲料组各时间点血清胰岛素均高于对照组,120 min时胰岛素浓度是对照组的6.3倍(P=0.008),胰岛和肝脏出现病理改变。结论 使用脂肪供能比为45%的高脂饲料喂养6周龄SD大鼠4周后淘汰OR大鼠,OB大鼠中出现糖耐量异常,8~12周后成模率更高。

Objective: To investigate the appropriate conditions and duration for establishing a high-fat diet-induced obesity and insulin resistance model in rats.Methods: Forty-five 6-week-old male Sprague-Dawley (SD) rats were randomly assigned into 2 groups: (1) control group (CON), (2) high-fat diet group (HFD). HFD was fed with a high-fat diet (45% kcal from fat) while CON with chow diet. After four-weeks of high-fat diet feeding, the rats of obesity resistance (OR) were eliminated according to body weight sorting, whereas obese (OB) rats were continued feeding a high-fat diet until 12 weeks. Body weight and food intake were recorded weekly. Glucose tolerance was evaluated by oral glucose tolerance test (OGTT) in 4 weeks, 8 weeks and 12 weeks. At the end of 12 weeks, insulin releasing test and visceral fat mass were measured and HE staining of the liver, adipose tissue and pancreatic tissue were conducted.Results: After 4 weeks of a high-fat diet, the body weight of HFD was 17.8% higher than that of CON (P=0.001), and the rate of obesity was 67.6%-78.4%. Glucose tolerance of OB rats was impaired with a higher blood glucose concentration at 120 min (P<0.001) and a higher area under the curve (AUC, P=0.037) in OGTT compared with CON. The rate of obesity and insulin-resistance rats was 79.3%. After 8 weeks of feeding, the body weight in OB was 30.4% higher than CON (P<0.001). In OGTT, blood glucose levels at 60 min and 120 min were 35.6% and 36.4% higher than those in CON (both P<0.001), and AUC was 21.7% (P<0.001) higher than that of CON. The rate of obesity and insulin-resistance rats was 100.0%. After 12 weeks of feeding, the body weight in OB was 36.9% higher than that in CON (P<0.001). In OGTT, the blood glucose levels at 60 min and 120 min were 24.8% (P=0.001) and 34.6% (P<0.001) higher than those in CON, and AUC was 16.1% (P=0.019) higher than that of CON. The rate of obesity and insulin-resistance rats was 93.3%. The insulin releasing test showed that serum insulin concentration at each time point (0, 30, 60, 120 min) was higher than that in CON, with a 6.3-times higher than that in CON at 120 min (P=0.008). Pathological changes were observed in islets and liver in the OB rats.Conclusion: After 4 weeks of a high-fat diet (45% kcal from fat) feeding in six-weeks SD rats, the rats of OR were eliminated. Impaired glucose tolerance was found in OB rats after 4 weeks of feeding, and the rate was higher after 8-12 weeks of high-fat diet feeding.