Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Cell Metab. 2011 Sep 7;14(3):313-23. doi: 10.1016/j.cmet.2011.06.016.
Leptin acts on leptin receptor (LepRb)-expressing neurons throughout the brain, but the roles for many populations of LepRb neurons in modulating energy balance and behavior remain unclear. We found that the majority of LepRb neurons in the lateral hypothalamic area (LHA) contain neurotensin (Nts). To investigate the physiologic role for leptin action via these LepRb(Nts) neurons, we generated mice null for LepRb specifically in Nts neurons (Nts-LepRbKO mice). Nts-LepRbKO mice demonstrate early-onset obesity, modestly increased feeding, and decreased locomotor activity. Furthermore, consistent with the connection of LepRb(Nts) neurons with local orexin (OX) neurons and the ventral tegmental area (VTA), Nts-LepRbKO mice exhibit altered regulation of OX neurons and the mesolimbic DA system. Thus, LHA LepRb(Nts) neurons mediate physiologic leptin action on OX neurons and the mesolimbic DA system, and contribute importantly to the control of energy balance.
瘦素作用于整个大脑中表达瘦素受体（LepRb）的神经元，但许多 LepRb 神经元群在调节能量平衡和行为方面的作用仍不清楚。我们发现，外侧下丘脑区域（LHA）的大多数 LepRb 神经元含有神经降压素（Nts）。为了研究通过这些 LepRb（Nts）神经元进行瘦素作用的生理作用，我们生成了 LepRb 特异性缺失 Nts 神经元的小鼠（Nts-LepRbKO 小鼠）。Nts-LepRbKO 小鼠表现出早发性肥胖、适度增加的摄食和减少的运动活性。此外，与 LepRb（Nts）神经元与局部食欲素（OX）神经元和腹侧被盖区（VTA）的连接一致，Nts-LepRbKO 小鼠表现出 OX 神经元和中脑边缘多巴胺系统的调节改变。因此，LHA LepRb（Nts）神经元介导瘦素对 OX 神经元和中脑边缘多巴胺系统的生理作用，并对能量平衡的控制起着重要作用。
