Leptin Suppresses the Rewarding Effects of Running via STAT3 Signaling in Dopamine Neurons
Leptin Suppresses the Rewarding Effects of Running via STAT3 Signaling in Dopamine Neurons
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DOI：
10.1016/j.cmet.2015.08.003
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发表时间：
2015-10-06
期刊：
影响因子：
29
通讯作者：
Fulton, Stephanie
中科院分区：
文献类型：
--
作者：
Fernandes, Maria Fernanda A.;Matthys, Dominique;Fulton, Stephanie
脂肪激素瘦素对身体活动有很大影响。瘦素可以减少运动和跑步，但所涉及的机制和瘦素对跑步奖励效应（“跑步者的快感”）的影响尚不清楚。瘦素受体（LepR）信号传导涉及信号换能器和转录激活因子-3 （STAT3）的激活，包括腹侧被盖区（VTA）的多巴胺神经元，这对奖励相关行为至关重要。我们发现多巴胺神经元中缺乏STAT3的小鼠表现出更大的自主奔跑，这种效应被病毒介导的STAT3恢复所逆转。STAT3缺失增加了跑步的奖励效果，而vta内瘦素以STAT3依赖的方式阻止了它。最后，STAT3功能丧失减少了中脑边缘多巴胺溢出和功能。研究结果表明，瘦素通过LepR-STAT3调节多巴胺音调来影响跑步的动机效应。瘦素的下降被假设为增加耐力和跑步的奖励效果，作为一种适应性手段来增强对食物的追求和获取。
The adipose hormone leptin potently influences physical activity. Leptin can decrease locomotion and running, yet the mechanisms involved and the influence of leptin on the rewarding effects of running ("runner's high'') are unknown. Leptin receptor (LepR) signaling involves activation of signal transducer and activator of transcription-3 (STAT3), including in dopamine neurons of the ventral tegmental area (VTA) that are essential for reward-relevant behavior. We found that mice lacking STAT3 in dopamine neurons exhibit greater voluntary running, an effect reversed by viral-mediated STAT3 restoration. STAT3 deletion increased the rewarding effects of running whereas intra-VTA leptin blocked it in a STAT3-dependent manner. Finally, STAT3 loss-of-function reduced mesolimbic dopamine overflow and function. Findings suggest that leptin influences the motivational effects of running via LepR-STAT3 modulation of dopamine tone. Falling leptin is hypothesized to increase stamina and the rewarding effects of running as an adaptive means to enhance the pursuit and procurement of food.