Håkansson M, de Lecea L, Sutcliffe J G, Yanagisawa M, Meister B
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
J Neuroendocrinol. 1999 Aug;11(8):653-63. doi: 10.1046/j.1365-2826.1999.00378.x.
Hypocretins/orexins are recently characterized peptides that are synthesized in neurones of the lateral hypohalamus and stimulate food intake in rats. To clarify whether leptin may interact with hypocretin/orexin to reduce ingestive behaviour, the presence of leptin receptor-immunoreactivity in hypocretin/orexin-containing neurones was examined. Many leptin receptor-and hypocretin/orexin-immunoreactive neurones were demonstrated in the lateral hypothalamic area and perifornical region. Both direct double-labelling and elution-restaining methods showed that leptin receptor-immunoreactivity was present in the vast majority of hypocretin/orexin-containing neurones. Immunoreactivity for STAT3, a transcription factor activated by leptin, was also demonstrated in hypocretin/orexin-containing neurones. Isolated hypocretin/orexin cell bodies in the dorsal part of the lateral hypothalamic area and the ventral perifornical region were shown to contain immunoreactivity for galanin, another peptide known to affect feeding. Galanin neurones were also seen to contain leptin receptor-and STAT3-immunoreactivity. Melanin-concentrating hormone (MCH)-containing neurones constituted a cell population within the lateral hypothalamus distinct from the one containing hypocretin/orexin-immunoreactivity, as shown by elution-restaining methodology. The presence of leptin receptor-and STAT3-immunoreactivities in hypocretin/orexin-containing neurones of the lateral hypothalamus suggests that leptin may directly regulate these hypothalamic neurones, most likely via an inhibitory action on hypocretin/orexin expression and/or secretion resulting in reduced food intake.
下丘脑泌素/食欲素是最近被鉴定出的一类肽，由下丘脑外侧区的神经元合成，并能刺激大鼠的食物摄取。为了阐明瘦素是否可能与下丘脑泌素/食欲素相互作用以减少摄食行为，研究人员检测了含下丘脑泌素/食欲素的神经元中瘦素受体免疫反应性的存在情况。在下丘脑外侧区和穹窿周区发现了许多瘦素受体和下丘脑泌素/食欲素免疫反应性神经元。直接双重标记法和洗脱后保留法均显示，绝大多数含下丘脑泌素/食欲素的神经元中存在瘦素受体免疫反应性。在含下丘脑泌素/食欲素的神经元中也证实了对瘦素激活的转录因子STAT3的免疫反应性。下丘脑外侧区背侧和穹窿腹侧区分离出的下丘脑泌素/食欲素细胞体显示含有甘丙肽的免疫反应性，甘丙肽是另一种已知会影响进食的肽。甘丙肽神经元也被发现含有瘦素受体和STAT3免疫反应性。洗脱后保留法显示，含黑色素浓缩激素（MCH）的神经元构成下丘脑外侧区内一个与含下丘脑泌素/食欲素免疫反应性的神经元群体不同的细胞群。下丘脑外侧区含下丘脑泌素/食欲素的神经元中存在瘦素受体和STAT3免疫反应性，这表明瘦素可能直接调节这些下丘脑神经元，很可能是通过对下丘脑泌素/食欲素表达和/或分泌的抑制作用，从而导致食物摄入量减少。
