Keen-Rhinehart Erin, Bartness Timothy J
Department of Biology, 24 Peachtree Center Ave. NE, Georgia State University, Atlanta, GA 30302-4010, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Apr;292(4):R1728-37. doi: 10.1152/ajpregu.00597.2006. Epub 2007 Jan 4.
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.
禁食会引发一系列生理和行为变化,包括外周产生的胃饥饿素和中枢产生的下丘脑神经肽Y(NPY)增加。再进食会刺激大多数物种的食物摄入;然而,仓鼠主要是增加觅食和食物囤积,食物摄入量增加较少。外周注射胃饥饿素、中枢注射NPY以及注射NPY Y1受体激动剂,均可模拟禁食诱导的西伯利亚仓鼠觅食和食物囤积增加。由于禁食会刺激胃饥饿素,随后刺激NPY的合成/释放,因此禁食诱导的囤积增加可能是由NPY Y1受体激活介导的。因此,我们提出疑问:Y1受体拮抗剂能否阻断禁食或胃饥饿素诱导的觅食、食物囤积和食物摄入量增加?这是通过在禁食、进食或接受外周胃饥饿素注射的仓鼠脑室内注射NPY Y1受体拮抗剂1229U91来实现的,这些仓鼠饲养在基于跑步轮的食物递送觅食系统中,并配有模拟洞穴的饲养环境。使用了三种觅食条件:1)无跑步轮,自由取食;2)有跑步轮,自由取食;或3)觅食要求(每获得一粒食物需转动10圈)。禁食比胃饥饿素更能有效地刺激觅食和食物囤积。同时注射1229U91完全阻断了禁食和胃饥饿素诱导的觅食和食物摄入量增加,并减弱了(但并不总是完全阻断)禁食和胃饥饿素诱导的食物囤积增加。总体而言,这些数据表明,NPY Y1受体对胃饥饿素和禁食诱导的觅食和食物摄入量增加的影响很重要,但其他NPY受体和/或其他神经化学系统参与了食物囤积的增加。