Zhu Y, Yamanaka A, Kunii K, Tsujino N, Goto K, Sakurai T
Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Physiol Behav. 2002 Nov;77(2-3):251-7. doi: 10.1016/s0031-9384(02)00843-0.
Orexin-A and -B are neuropeptides that are implicated in the regulation of vigilance states and energy homeostasis. Orexins are specifically produced by neurons located within the lateral hypothalamic area (LHA), a region implicated in the regulation of feeding behavior. Here, we examined the functional interactions between orexins and anorectic factors [leptin, alpha-melanocyte-stimulating hormone (alpha-MSH) and glucagon-like peptide-1 (GLP-1)] in rats. Intracerebroventricular injection of orexin-A (10 nmol) potently augmented food intake in rats. Neuropeptide Y (NPY) (0.3 nmol) and galanin (3 nmol) also induced a transient increase in food intake. Both NPY- and galanin-induced feeding behaviors were completely inhibited by preadministration of leptin (3 microg), while the same or a higher dose (10 microg) of leptin only partially inhibited orexin-A or -B-induced increase of food intake. Preadministration of anorectic peptides (alpha-MSH and GLP-1), which are shown to be regulated by leptin, abolished NPY-induced feeding; however, orexin-induced feeding was only partially inhibited by these anorectic peptides. These observations suggest that NPY- and galanin-induced increases of feeding involve a leptin-sensitive pathway, while orexin-induced feeding involves both leptin-sensitive and -insensitive pathways.
食欲素A和食欲素B是与警觉状态和能量平衡调节有关的神经肽。食欲素由位于下丘脑外侧区（LHA）的神经元特异性产生，该区域与进食行为的调节有关。在此，我们研究了大鼠体内食欲素与厌食因子[瘦素、α-黑素细胞刺激素（α-MSH）和胰高血糖素样肽-1（GLP-1）]之间的功能相互作用。脑室内注射食欲素A（10 nmol）可显著增加大鼠的食物摄入量。神经肽Y（NPY）（0.3 nmol）和甘丙肽（3 nmol）也会引起食物摄入量的短暂增加。预先给予瘦素（3μg）可完全抑制NPY和甘丙肽诱导的进食行为，而相同剂量或更高剂量（10μg）的瘦素仅部分抑制食欲素A或食欲素B诱导的食物摄入量增加。预先给予已证明受瘦素调节的厌食肽（α-MSH和GLP-1）可消除NPY诱导的进食；然而，这些厌食肽仅部分抑制食欲素诱导的进食。这些观察结果表明，NPY和甘丙肽诱导的进食增加涉及一条瘦素敏感途径，而食欲素诱导的进食涉及瘦素敏感和不敏感两条途径。
