Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
Mol Metab. 2013 Aug 7;2(4):423-34. doi: 10.1016/j.molmet.2013.07.008. eCollection 2013.
Neurons of the lateral hypothalamic area (LHA) control motivated behaviors such as feeding and ambulatory activity, in part by modulating mesolimbic dopamine (DA) circuits. The hormone, leptin, acts via the long form of the leptin receptor (LepRb) in the brain to signal the repletion of body energy stores, thereby decreasing feeding and promoting activity. LHA LepRb neurons, most of which contain neurotensin (Nts; LepRb(Nts) neurons) link leptin action to the control of mesolimbic DA function and energy balance. To understand potential roles for Nts in these processes, we examined mice null for Nts receptor 1 (NtsR1KO). While NtsR1KO mice consume less food than controls on a chow diet, they eat more and become obese when fed a high-fat, high-sucrose palatable diet; NtsR1KO mice also exhibit augmented sucrose preference, consistent with increased hedonic feeding in these animals. We thus sought to understand potential roles for NtsR1 in the control of the mesolimbic DA system and LHA leptin action. LHA Nts cells project to DA-containing midbrain areas, including the ventral tegmental area (VTA) and the substantia nigra (SN), where many DA neurons express NtsR1. Furthermore, in contrast to wild-type mice, intra-LHA leptin treatment increased feeding and decreased VTA Th expression in NtsR1KO mice, consistent with a role for NtsR1 signaling from LHA LepRb neurons in the suppression of food intake and control of mesolimbic DA function. Additionally, these data suggest that other leptin-regulated LHA neurotransmitters normally oppose aspects of Nts action to promote balanced responses to leptin.
外侧下丘脑区域（LHA）的神经元控制着摄食和活动等动机行为，部分是通过调节中脑边缘多巴胺（DA）回路。激素瘦素通过脑内长形式瘦素受体（LepRb）作用，提示身体能量储存的恢复，从而减少摄食并促进活动。LHA LepRb 神经元，其中大多数含有神经降压素（Nts；LepRb(Nts)神经元），将瘦素作用与中脑边缘 DA 功能和能量平衡的控制联系起来。为了了解 Nts 在这些过程中的潜在作用，我们研究了缺乏 Nts 受体 1（NtsR1KO）的小鼠。虽然 NtsR1KO 小鼠在标准饮食下的食物摄入量低于对照组，但当喂食高脂肪、高蔗糖的美味饮食时，它们会吃得更多并变得肥胖；NtsR1KO 小鼠也表现出蔗糖偏好增加，与这些动物的快感进食增加一致。因此，我们试图了解 NtsR1 在中脑边缘 DA 系统和 LHA 瘦素作用控制中的潜在作用。LHA Nts 细胞投射到含有 DA 的中脑区域，包括腹侧被盖区（VTA）和黑质（SN），其中许多 DA 神经元表达 NtsR1。此外，与野生型小鼠相比，LHA 内瘦素处理增加了 NtsR1KO 小鼠的摄食并减少了 VTA Th 的表达，这与来自 LHA LepRb 神经元的 NtsR1 信号在抑制摄食和控制中脑边缘 DA 功能中的作用一致。此外，这些数据表明，其他瘦素调节的 LHA 神经递质通常会拮抗 Nts 作用的某些方面，以促进对瘦素的平衡反应。
