Melanin-concentrating hormone receptor is a target of leptin action in the mouse brain
Melanin-concentrating hormone receptor is a target of leptin action in the mouse brain
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DOI：
10.1210/en.142.2.680
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发表时间：
2001-02-01
期刊：
影响因子：
4.8
通讯作者：
Maratos-Flier, E
中科院分区：
文献类型：
--
作者：
Kokkotou, EG;Tritos, NA;Maratos-Flier, E
黑色素浓集激素（MCH）是一种下丘脑神经肽，在能量稳态调节中起重要作用。MCH通过一个七跨膜G蛋白偶联受体（与G α（i）偶联）发出信号。该受体最初在大鼠和人中克隆，并由于其与生长抑素受体同源而命名为SLC-1。在大鼠脑中，它的表达模式反映了先前描述的MCH免疫反应性纤维的投射模式。在本研究中，我们克隆了小鼠MCH受体（MCH-R）的直系同源物的5 '-和3'-cDNA末端的快速扩增方法，并发现它与大鼠序列的同源性为98%。我们已经通过原位杂交表征了MCH-R信使RNA在小鼠脑中的分布，并且已经表明MCH-R在涉及摄食调节、身体肥胖以及嗅觉和味觉输入的感觉整合的不同脑区中表达，包括下丘脑[室旁核（大细胞部分）和背内侧、腹内侧和弓状核]，嗅觉通路的区域，我们还研究了MCH-R的调节，发现MCH-R的表达通过48小时禁食或遗传性瘦素缺乏（ob/ob小鼠）增加7倍，并且通过给予瘦素完全钝化。相比之下，MCH-R信使RNA表达在遗传MCH缺乏症中保持不变。我们的研究结果表明，MCH-R构成了哺乳动物大脑中瘦素作用的中心靶点。
Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that is important in the regulation of energy homeostasis. MCH signals via a seven-transmembrane G protein-coupled receptor, which is coupled to G alpha (i). This receptor was initially cloned in rat and human and designated SLC-1 because of its homology to the somatostatin receptor. In rat brain, it is expressed in a pattern that mirrors the previously described pattern of projections of MCH-immunoreactive fibers.In the present study we cloned the mouse MCH receptor (MCH-R) ortholog by a rapid amplification of 5'- and 3'-cDNA ends approach and have found it to be 98% homologous with the rat sequence. We have characterized MCH-R messenger RNA distribution in the mouse brain by in situ hybridization and have shown MCH-R to be expressed in diverse brain areas implicated in the regulation of feeding, body adiposity, and sensory integration of smell and gustatory inputs, including the hypothalamus [paraventricular nucleus (magnocellular part) and dorsomedial, ventromedial, and arcuate nucleus], areas of the olfactory pathway, and the nucleus of the solitary tract.We also studied MCH-R regulation and found that MCH-R expression is increased 7-fold by 48-h fasting or genetic leptin deficiency (ob/ob mice) and is completely blunted by leptin administration. In contrast, MCH-R messenger RNA expression remains unaltered in genetic MCH deficiency. Our findings suggest that MCH-R constitutes a central target of leptin action in the mammalian brain.