Leptin receptor signaling in midbrain dopamine neurons regulates feeding
Leptin receptor signaling in midbrain dopamine neurons regulates feeding
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DOI：
10.1016/j.neuron.2006.08.023
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发表时间：
2006-09-21
期刊：
影响因子：
16.2
通讯作者：
DiLeone, Ralph J.
中科院分区：
文献类型：
--
作者：
Hommel, Jonathan D.;Trinko, Richard;DiLeone, Ralph J.
瘦素激素对正常的食物摄入和新陈代谢至关重要。虽然瘦素受体（Lept）的功能已经在下丘脑中得到了很好的研究，但腹侧被盖区（VTA）中Lepr表达的功能相关性尚未研究。腹侧被盖区含有多巴胺神经元，这些神经元在调节动机行为、成瘾和奖励方面非常重要。在这里，我们表明，腹侧被盖区多巴胺神经元表达Lepr mRNA和响应瘦素与细胞内JAK-STAT通路的激活和放电率的降低。直接给予腹侧被盖区瘦素导致食物摄入减少，而长期RNAi介导的腹侧被盖区瘦素敲低导致食物摄入增加、运动活动增加和对高可口食物的敏感性增加。这些数据支持腹侧被盖区Lepr在调节摄食行为中的关键作用，并为外周代谢信号对腹侧被盖区多巴胺神经元的直接作用提供了功能证据。
The leptin hormone is critical for normal food intake and metabolism. While leptin receptor (Lept) function has been well studied in the hypothalamus, the functional relevance of Lepr expression in the ventral tegmental area (VTA) has not been investigated. The VTA contains dopamine neurons that are important in modulating motivated behavior, addiction, and reward. Here, we show that VTA dopamine neurons express Lepr mRNA and respond to leptin with activation of an intracellular JAK-STAT pathway and a reduction in firing rate. Direct administration of leptin to the VTA caused decreased food intake while long-term RNAi-mediated knockdown of Lepr in the VTA led to increased food intake, locomotor activity, and sensitivity to highly palatable food. These data support a critical role for VTA Lepr in regulating feeding behavior and provide functional evidence for direct action of a peripheral metabolic signal on VTA dopamine neurons.