Akiyama T, Tachibana I, Shirohara H, Watanabe N, Otsuki M
Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu, Japan.
Diabetes Res Clin Pract. 1996 Mar;31(1-3):27-35. doi: 10.1016/0168-8227(96)01205-3.
There is strong evidence that genetic factors contribute to the development of obesity in humans as well as laboratory animals. Another important factor leading to obesity is an increase in energy intake. However, it is difficult to make normal rats obese by controlling daily food intake. There is no report of normal adult male Wistar rats becoming obese and diabetic on a high-fat diet. The aim of the present study was, therefore, to make normal adult Wistar rats obese by infusing high fat and hypercaloric diet through the cannula without disturbing the free movement and to investigate the influence of an increase in the caloric intake on body weight and glucose metabolism. High-fat hypercaloric diet (360 kcal/kg body wt./day; H group) or control diet (180 kcal/kg body wt./day; C group) was continuously infused into the stomach of normal adult male Wistar rats weighing approximately 300 g through gastric cannulas for 27 days. On day 28 after a 24-h fasting, serum concentrations of aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglyceride, phospholipid, and free fatty acids (FFA) were determined, and intragastric glucose loading test (2 g/kg body wt.) was performed. The average weekly body weight gain in the H group was twice as much as that of the C group (40.0 +/- 2.4 vs. 19.4 +/- 1.9 g/week, P < 0.001). Serum levels of triglyceride, phospholipid, total cholesterol, and FFA were significantly elevated in the H group compared to those in the C group. Liver weight in the H group was significantly higher than that in the C group and showed steatosis. Pancreas weight (-13%) as well as protein (-12%), amylase (-53%) and trypsin content (-26%) were all reduced, whereas pancreatic DNA content was significantly increased in the H group compared to those in the C group. Serum glucose and insulin concentrations before and after glucose loading in the H group were significantly higher than those in the C group. Moreover, the insulin response relative to glucose response in the H group was significantly high compared to that in the C group, indicating the presence of insulin resistance. These results indicate that feeding of high-fat hypercaloric diet makes normal Wistar male adult rat obese associated with hyperlipidemia, hyperinsulinemia, and glucose intolerance.
有充分证据表明，遗传因素在人类以及实验动物肥胖症的发生发展中起作用。导致肥胖的另一个重要因素是能量摄入增加。然而，通过控制每日食物摄入量很难使正常大鼠肥胖。尚无正常成年雄性Wistar大鼠在高脂饮食下变得肥胖和患糖尿病的报道。因此，本研究的目的是通过插管输注高脂高热量饮食，在不干扰自由活动的情况下使正常成年Wistar大鼠肥胖，并研究热量摄入增加对体重和葡萄糖代谢的影响。通过胃插管将高脂高热量饮食（360千卡/千克体重/天；H组）或对照饮食（180千卡/千克体重/天；C组）持续输注到体重约300克的正常成年雄性Wistar大鼠胃内，持续27天。在禁食24小时后的第28天，测定血清天冬氨酸转氨酶、丙氨酸转氨酶、总胆固醇、甘油三酯、磷脂和游离脂肪酸（FFA）的浓度，并进行胃内葡萄糖负荷试验（2克/千克体重）。H组平均每周体重增加量是C组的两倍（40.0±2.4对19.4±1.9克/周，P<0.001）。与C组相比，H组血清甘油三酯、磷脂、总胆固醇和FFA水平显著升高。H组肝脏重量显著高于C组，并出现脂肪变性。H组胰腺重量（-13%）以及蛋白质（-12%）、淀粉酶（-53%）和胰蛋白酶含量（-26%）均降低，而胰腺DNA含量与C组相比显著增加。H组葡萄糖负荷前后的血清葡萄糖和胰岛素浓度显著高于C组。此外，与C组相比，H组相对于葡萄糖反应的胰岛素反应显著升高，表明存在胰岛素抵抗。这些结果表明，高脂高热量饮食喂养使正常Wistar成年雄性大鼠肥胖，伴有高脂血症、高胰岛素血症和葡萄糖不耐受。
