Qu D, Ludwig D S, Gammeltoft S, Piper M, Pelleymounter M A, Cullen M J, Mathes W F, Przypek R, Kanarek R, Maratos-Flier E
Elliott P. Joslin Research Laboratory, Joslin Diabetes Center, Boston, MA, USA.
Nature. 1996 Mar 21;380(6571):243-7. doi: 10.1038/380243a0.
The hypothalamus plays a central role in the integrated regulation of energy homeostasis and body weight, and a number of hypothalamic neuropeptides, such as neuropeptide Y (ref. 1), galanin, CRH (ref. 3) and GLP-1 (ref. 4), have been implicated in the mediation of these effects. To discover new hypothalmic peptides involved in the regulation of body weight, we used differential display polymerase chain reaction to identify messenger RNAs that are differentially expressed in the hypothalamus of ob/+ compared with ob/ob C57B1/6J mice. We show here that one mRNA that is overexpressed in the hypothalamus of ob/ob mice encodes the neuropeptide melanin-concentrating hormone (MCH). Fasting further increased expression of MCH mRNA in both normal and obese animals. Neurons containing MCH are located in the zona incerta and in the lateral hypothalamus. These areas are involved in regulation of ingestive behaviour, but the role of MCH in mammalian physiology is unknown. To determine whether MCH is involved in the regulation of feeding, we injected MCH into the lateral ventricles of rats and found that their food consumption increased. These findings suggest that MCH participates in the hypothalamic regulation of body weight.
下丘脑在能量平衡和体重的整合调节中起核心作用，一些下丘脑神经肽，如神经肽Y（参考文献1）、甘丙肽、促肾上腺皮质激素释放激素（参考文献3）和胰高血糖素样肽-1（参考文献4），都与这些作用的介导有关。为了发现参与体重调节的新的下丘脑肽，我们使用差异显示聚合酶链反应来鉴定在ob/+与ob/ob C57B1/6J小鼠下丘脑中有差异表达的信使核糖核酸。我们在此表明，在ob/ob小鼠下丘脑中过度表达的一种信使核糖核酸编码神经肽黑色素浓集激素（MCH）。禁食进一步增加了正常和肥胖动物体内MCH信使核糖核酸的表达。含有MCH的神经元位于未定带和下丘脑外侧区。这些区域参与摄食行为的调节，但MCH在哺乳动物生理学中的作用尚不清楚。为了确定MCH是否参与进食调节，我们将MCH注射到大鼠侧脑室，发现它们的食物消耗量增加。这些发现表明，MCH参与下丘脑对体重的调节。
