Institute of Veterinary Physiology and Zurich Center for Integrative Human Physiology, Vetsuisse Faculty University of Zürich, Switzerland.
Physiol Behav. 2011 Jul 25;104(1):20-8. doi: 10.1016/j.physbeh.2011.04.044. Epub 2011 May 3.
Obesity results in the increased secretion of various hormones controlling food intake and body weight, such as leptin, and insulin; increased circulating levels of pancreatic amylin have also been described in obese humans and rodents. Because leptin-resistance is present in diet-induced obese (DIO) rats, and because hyperleptinemia seems necessary for the full development of leptin resistance, we tested whether amylin sensitivity is inversely correlated with adiposity, such that DIO reduces the anorectic action of acute amylin. We also determined if hyperamylinemia leads to a change in amylin sensitivity. In the first experiment, rats were chronically exposed to a high fat (HF; 60% fat) diet or fed standard chow for control. The anorectic response to amylin was tested on several occasions over a 14 week observation period. HF feeding led to the expected increase in body adiposity; the response to an acute amylin injection (5-50 μg/kg s.c.) was unaltered for 10 weeks of HF feeding. Even after 12 weeks on a HF diet, which clearly caused obesity, acute administration of amylin (5 μg/kg, s.c.) was still able to suppress food intake, although the suppression was not statistically significant. Further experiments using additional doses of amylin will be necessary to demonstrate possible amylin resistance after HF feeding or in DIO rats. In the second experiment, we tested more specifically whether hyperamylinemia that may result from HF feeding and subsequent obesity, reduces the sensitivity of the amylin signaling system. To avoid confounding factors, we chronically infused lean chow fed rats with amylin (5 or 10 μg/kg/day s.c.) to elevate their plasma amylin concentration to levels observed in obese rats (30-40 pM). In the absence of obesity, hyperamylinemia did not lead to a reduced sensitivity to acute amylin (5-20 μg/kg s.c.) injections; acute amylin reduced eating similarly in all groups of rats. Overall, we concluded that direct diet effects by short term exposure to HF appear to be of little importance for amylin sensitivity; further, long-term maintenance on a HF diet and the resulting obesity only slightly attenuated the anorectic response to acute amylin. Because we observed no marked changes in amylin sensitivity in lean, chow fed rats with induced hyperamylinemia, amylin receptor downregulation in chronic hyperamylinemia does not seem to occur.
肥胖会导致控制食物摄入和体重的各种激素分泌增加，如瘦素和胰岛素；肥胖人群和肥胖啮齿动物的循环中胰腺淀粉酶水平也升高。由于饮食诱导肥胖（DIO）大鼠存在瘦素抵抗，并且似乎需要高瘦素血症才能完全发展出瘦素抵抗，因此我们测试了淀粉酶的敏感性是否与肥胖程度呈反比，即 DIO 会降低急性淀粉酶的厌食作用。我们还确定了高淀粉酶血症是否会导致淀粉酶敏感性的变化。在第一个实验中，大鼠长期暴露于高脂肪（HF；60%脂肪）饮食或标准饲料中作为对照。在 14 周的观察期内，多次测试了对淀粉酶的厌食反应。HF 喂养导致预期的体脂增加；在 HF 喂养 10 周时，对急性淀粉酶注射（5-50μg/kg sc）的反应没有改变。即使在 HF 饮食 12 周后，即明显肥胖后，急性给予淀粉酶（5μg/kg，sc）仍能抑制进食，尽管抑制作用无统计学意义。使用淀粉酶的其他剂量进行进一步实验将有助于证明 HF 喂养或 DIO 大鼠后可能存在淀粉酶抵抗。在第二个实验中，我们更具体地测试了 HF 喂养和随后肥胖可能导致的高淀粉酶血症是否降低了淀粉酶信号系统的敏感性。为了避免混杂因素，我们对长期喂养标准饲料的大鼠慢性输注淀粉酶（5 或 10μg/kg/天 sc），将其血浆淀粉酶浓度升高至肥胖大鼠（30-40 pM）观察到的水平。在没有肥胖的情况下，高淀粉酶血症不会导致对急性淀粉酶（5-20μg/kg sc）注射的敏感性降低；急性淀粉酶对所有大鼠组的进食均有相似的抑制作用。总体而言，我们得出结论，短期暴露于 HF 的直接饮食影响对淀粉酶敏感性似乎不重要；此外，长期维持 HF 饮食和由此导致的肥胖仅略微减弱了对急性淀粉酶的厌食反应。由于我们在诱导高淀粉酶血症的瘦、标准饲料喂养大鼠中没有观察到淀粉酶敏感性的明显变化，因此在慢性高淀粉酶血症中似乎不会发生淀粉酶受体下调。
