Centre de Recherche du CHUM and Montreal Diabetes Research Center, Université de Montreal, QC H2X 0A9, Canada; Department of Physiology, Université de Montreal, QC H2X 0A9, Canada.
Centre de Recherche du CHUM and Montreal Diabetes Research Center, Université de Montreal, QC H2X 0A9, Canada; Department of Neuroscience, Université de Montreal, QC H2X 0A9, Canada.
Cell Metab. 2015 Oct 6;22(4):741-9. doi: 10.1016/j.cmet.2015.08.003. Epub 2015 Sep 1.
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.
脂肪激素瘦素强烈影响身体活动。瘦素可以减少运动和跑步，但涉及的机制以及瘦素对跑步的奖励效应（“跑步者的快感”）尚不清楚。瘦素受体（LepR）信号涉及信号转导子和转录激活子 3（STAT3）的激活，包括腹侧被盖区（VTA）的多巴胺神经元，这对于奖励相关行为至关重要。我们发现，缺乏多巴胺神经元中的 STAT3 的小鼠表现出更多的自愿跑步，而通过病毒介导的 STAT3 恢复可以逆转这种效果。STAT3 缺失增加了跑步的奖励效应，而 VTA 内的瘦素以 STAT3 依赖性方式阻断了它。最后，STAT3 功能丧失减少了中脑边缘多巴胺的溢出和功能。研究结果表明，瘦素通过 LepR-STAT3 调节多巴胺张力来影响跑步的动机效应。假设瘦素下降会增加耐力和跑步的奖励效应，作为一种增强对食物的追求和获取的适应性手段。
