Hollopeter G, Erickson J C, Seeley R J, Marsh D J, Palmiter R D
Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle 98195, USA.
Regul Pept. 1998 Sep 25;75-76:383-9. doi: 10.1016/s0167-0115(98)00092-5.
Neuropeptide Y (NPY) is thought to be an important central regulator of feeding behavior and body weight. However, mice lacking NPY due to targeted genetic deletion do not display abnormalities in food intake or body weight with ad libitum access to food or in response to fasting. In this study, we investigate the response of NPY-deficient (NPY-/-) mice to anorexic and orexigenic treatments. The dose-dependent stimulation of food intake by central NPY administration was unaltered in NPY-/- mice. Peripheral administration of various doses of leptin for 2 days elicited a two-fold greater inhibition of food intake in NPY-/- mice than in wildtype (NPY+/+) mice. In addition, lateral ventricular administration of leptin (1 microg) suppressed refeeding in NPY-/- mice after a 24 h fast, but had little effect in NPY+/+ mice. However, the response to other feeding inhibitors such as corticotrophin releasing factor (CRF), dexfenfluramine, and a melanocortin 4 receptor (MC4R) agonist, MTII, was unaltered in NPY-/- mice. These results indicate that the appetite-suppressant action of exogenous leptin is uniquely amplified in NPY-/- mice, and suggest that NPY may tonically antagonize leptin action.
神经肽Y（NPY）被认为是进食行为和体重的重要中枢调节因子。然而，由于靶向基因缺失而缺乏NPY的小鼠在随意进食或禁食时，食物摄入量或体重并未表现出异常。在本研究中，我们调查了NPY缺陷型（NPY-/-）小鼠对厌食和促食欲治疗的反应。在NPY-/-小鼠中，中枢给予NPY对食物摄入量的剂量依赖性刺激未发生改变。外周给予不同剂量的瘦素2天，NPY-/-小鼠的食物摄入量受到的抑制比野生型（NPY+/+）小鼠大两倍。此外，侧脑室注射瘦素（1微克）可抑制NPY-/-小鼠禁食24小时后的重新进食，但对NPY+/+小鼠几乎没有影响。然而，NPY-/-小鼠对其他进食抑制剂如促肾上腺皮质激素释放因子（CRF）、右芬氟拉明和黑皮质素4受体（MC4R）激动剂MTII的反应未发生改变。这些结果表明，外源性瘦素的食欲抑制作用在NPY-/-小鼠中被独特地放大，提示NPY可能持续拮抗瘦素的作用。
