NPYY1 receptor is involved in ghrelin- and fasting-induced increases in foraging, food hoarding, and food intake
NPYY1 receptor is involved in ghrelin- and fasting-induced increases in foraging, food hoarding, and food intake
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DOI：
10.1152/ajpregu.00597.2006
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发表时间：
2007-04-01
影响因子：
2.8
通讯作者：
Bartness, Timothy J.
中科院分区：
文献类型：
--
作者：
Keen-Rhinehart, Erin;Bartness, Timothy J.
禁食引发一系列生理和行为变化，包括外周产生的ghrelin和中枢产生的下丘脑神经肽Y（NPY）的增加。再喂食刺激大多数物种的食物摄入;然而，仓鼠主要增加觅食和食物囤积，食物摄入量增加较少。禁食诱导的增加觅食和食物囤积在西伯利亚仓鼠是模仿外周生长激素释放肽，中央神经肽Y和神经肽Y Y1受体激动剂注射。因为禁食刺激ghrelin和随后的NPY合成/释放，所以禁食诱导的囤积增加可能是由NPY Y1受体激活介导的。因此，我们问：Y1受体拮抗剂能否阻断禁食或ghrelin诱导的觅食、食物囤积和食物摄入的增加？这是通过在禁食、进食或给予外周生长激素释放肽注射的仓鼠中脑室内注射NPY Y1受体拮抗剂1229 U91来实现的，并将其安置在与模拟洞穴住房相结合的基于转轮的食物递送觅食系统中。使用三种觅食条件：1）没有转轮进入，自由食物，2）转轮进入，自由食物，或3）食物的觅食要求（10转/颗粒）。禁食比饥饿激素更能刺激觅食和囤积食物。同时注射1229 U91完全阻断了禁食和生长激素释放肽诱导的觅食和食物摄入增加，并减弱了禁食和生长激素释放肽诱导的食物囤积增加，但并不总是完全阻断。总的来说，这些数据表明，神经肽Y 1受体是重要的生长激素释放肽和禁食诱导的觅食和食物摄入量的增加的影响，但其他神经肽Y受体和/或其他神经化学系统参与增加食物囤积。
Fasting triggers a constellation of physiological and behavioral changes, including increases in peripherally produced ghrelin and centrally produced hypothalamic neuropeptide Y (NPY). Refeeding stimulates food intake in most species; however, hamsters primarily increase foraging and food hoarding with smaller increases in food intake. Fasting-induced increases in foraging and food hoarding in Siberian hamsters are mimicked by peripheral ghrelin, central NPY, and NPY Y1 receptor agonist injections. Because fasting stimulates ghrelin and subsequently NPY synthesis/release, it may be that fasting-induced increased hoarding is mediated by NPY Y1 receptor activation. Therefore, we asked: Can an Y1 receptor antagonist block fasting- or ghrelin-induced increases in foraging, food hoarding, and food intake? This was accomplished by injecting the NPY Y1 receptor antagonist 1229U91 intracerebroventricularly in hamsters fasted, fed, or given peripheral ghrelin injections and housed in a running wheel-based food delivery foraging system coupled with simulated-burrow housing. Three foraging conditions were used: 1) no running wheel access, free food, 2) running wheel access, free food, or 3) foraging requirement (10 revolutions/pellet) for food. Fasting was a more potent stimulator of foraging and food hoarding than ghrelin. Concurrent injections of 1229U91 completely blocked fasting- and ghrelin-induced increased foraging and food intake and attenuated, but did not always completely block, fasting- and ghrelin-induced increases in food hoarding. Collectively, these data suggest that the NPY Y1 receptor is important for the effects of ghrelin- and fasting-induced increases in foraging and food intake, but other NPY receptors and/or other neurochemical systems are involved in increases in food hoarding.