Leinninger Gina M, Jo Young-Hwan, Leshan Rebecca L, Louis Gwendolyn W, Yang Hongyan, Barrera Jason G, Wilson Hilary, Opland Darren M, Faouzi Miro A, Gong Yusong, Jones Justin C, Rhodes Christopher J, Chua Streamson, Diano Sabrina, Horvath Tamas L, Seeley Randy J, Becker Jill B, Münzberg Heike, Myers Martin G
Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Cell Metab. 2009 Aug;10(2):89-98. doi: 10.1016/j.cmet.2009.06.011.
The lateral hypothalamic area (LHA) acts in concert with the ventral tegmental area (VTA) and other components of the mesolimbic dopamine (DA) system to control motivation, including the incentive to feed. The anorexigenic hormone leptin modulates the mesolimbic DA system, although the mechanisms underlying this control have remained incompletely understood. We show that leptin directly regulates a population of leptin receptor (LepRb)-expressing inhibitory neurons in the LHA and that leptin action via these LHA LepRb neurons decreases feeding and body weight. Furthermore, these LHA LepRb neurons innervate the VTA, and leptin action on these neurons restores VTA expression of the rate-limiting enzyme in DA production along with mesolimbic DA content in leptin-deficient animals. Thus, these findings reveal that LHA LepRb neurons link anorexic leptin action to the mesolimbic DA system.
外侧下丘脑区域（LHA）与腹侧被盖区（VTA）及中脑边缘多巴胺（DA）系统的其他组成部分协同作用，以控制动机，包括进食动机。厌食激素瘦素调节中脑边缘DA系统，尽管这种控制的潜在机制仍未完全明确。我们发现，瘦素直接调节LHA中一群表达瘦素受体（LepRb）的抑制性神经元，且通过这些LHA LepRb神经元的瘦素作用会减少进食量和体重。此外，这些LHA LepRb神经元支配VTA，瘦素对这些神经元的作用可恢复DA生成限速酶在VTA中的表达以及瘦素缺乏动物的中脑边缘DA含量。因此，这些发现揭示了LHA LepRb神经元将厌食性瘦素作用与中脑边缘DA系统联系起来。
