The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema nucleus of the solitary tract (AP/NTS) lesioned rats
The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema nucleus of the solitary tract (AP/NTS) lesioned rats
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DOI：
10.1038/sj.ijo.0801664
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发表时间：
2001-07-01
影响因子：
4.9
通讯作者：
Scharrer, E
中科院分区：
文献类型：
--
作者：
Lutz, TA;Mollet, A;Scharrer, E
目的：低剂量（5杯/千克）单次腹腔注射胰淀素后/孤束核区（AP/NTS）神经元介导胰淀素的厌食作用。在这里，我们测试了慢性胰淀素输注所达到的胰淀素水平的持续升高是否通过作用于AP/NTS区域或可能作用于其他大脑部位来减少食物摄入。此外，我们测试了AP/NTS区域在急性单次注射高剂量胰淀粉及其受体激动剂鲑鱼降钙素（sCT）后介导厌食效应中的作用。设计：在AP/ nts损伤（AP- x）或假性损伤（SHAM）大鼠中，通过渗透微型泵长期滴注胰淀素（2杯/kg/h）。急性实验中，胰淀素或sCT分别以0.5（仅sCT）、5或50马克杯/公斤的剂量腹腔注射。食物摄取量由电脑系统测量。用人工称重法测定大鼠体重。结果：胰淀素显著减少SHAM大鼠约7天的累积食物摄入量，但在AP-X大鼠中没有。胰淀素在SHAM大鼠中的作用主要是由于夜间摄食量的减少（例如，前四个黑暗期的平均摄食量；SHAM, NaCl 4.1 +/- 0.6 vs胰淀素2.6 +/- 0.4 g; n=6, P < 0.05; AP-X, 2.6 0.3 vs 3.7 +/- 0.3），而光照期的摄食量不受影响。在整个14天的输注期内，SHAM大鼠的体重增加被amylin减少（NaCl 61 +/- 6 vs amylin 46 +/- 4 g; P < 0.05），但AP-X大鼠没有（54.4 vs 62 +/- 4）。单次注射后，在AP-X大鼠中，高剂量amylin和sCT（50马克杯/千克）的厌食作用减弱，但未完全消除。结论：在我们的实验条件下，AP/NTS区域的神经元是大鼠慢性升高的外周胰淀素减少食物摄入所必需的。然而，高剂量的amylin可能会超过这些受体，并通过作用于大脑的其他部位来减少摄食。
OBJECTIVE: Neurons in the area postrema/nucleus of the solitary tract (AP/NTS) region mediate amylin's anorectic effect elicited by a single intraperitoneal (i.p.) injection of a low dose (5 mug/kg). Here, we tested if a sustained elevation in amylin levels which was achieved by chronic amylin infusion reduces food intake by acting in the AP/NTS region or, possibly, at other brain sites. Further, we tested the role of the AP/NTS region in mediating the anorectic effects of high doses of amylin and its receptor agonist salmon calcitonin (sCT) after an acute single injection.DESIGN: Amylin (2 mug/kg/h) was chronically infused i.p. by osmotic minipumps in AP/NTS-lesioned (AP-X) or sham-lesioned (SHAM) rats. For the acute experiments, amylin or sCT was injected i.p. at doses of 0.5 (only sCT), 5 or 50 mug/kg. Food intake was measured by a computerized system. Body weight was assessed by manually weighing the rats.RESULTS: Amylin significantly reduced cumulative food intake for about 7 days in SHAM but not in AP-X rats. Amylin's effect in SHAM rats was mainly due to a reduction of the size of nocturnal meals (eg average meal size during the first four dark phases; SHAM, NaCl 4.1 +/- 0.6 vs amylin 2.6 +/- 0.4 g; n=6, P < 0.05; AP-X, 2.6 0.3 vs 3.7 +/- 0.3) while light phase food intake was unaffected. Body weight gain over the whole 14 day infusion period was reduced by amylin in SHAM (NaCl 61 +/- 6 vs amylin 46 +/- 4 g; P < 0.05) but not in AP-X rats (54 4 vs 62 +/- 4). After single injection, the anorectic effect of high doses of amylin and sCT (50 mug/kg) was attenuated, but not abolished, in AP-X rats.CONCLUSION: We conclude that, under our experimental conditions, neurons in the AP/NTS region are necessary for chronically elevated peripheral amylin to reduce food intake in rats. High doses of amylin, however, may be able to overrun these receptors and reduce feeding by acting at other brain sites.