Hypothalamic melanin concentrating hormone neurons communicate the nutrient value of sugar.
Hypothalamic melanin concentrating hormone neurons communicate the nutrient value of sugar.
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DOI：
10.7554/elife.01462
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发表时间：
2013-12-31
期刊：
影响因子：
7.7
通讯作者：
Friedman JM
中科院分区：
文献类型：
--
作者：
Domingos AI;Sordillo A;Dietrich MO;Liu ZW;Tellez LA;Vaynshteyn J;Ferreira JG;Ekstrand MI;Horvath TL;de Araujo IE;Friedman JM
含有葡萄糖的糖，如蔗糖，通常比人工甜味剂更受欢迎，因为它们具有摄食后奖励作用，可提高纹状体多巴胺（DA）的释放。虽然人工甜味剂不具有的摄入后奖励效应发出了糖的营养价值并影响食物偏好的信号，但介导葡萄糖奖励效应的神经回路尚不清楚。在这项研究中，我们发现，在摄入人工甜味剂三氯蔗糖的过程中，黑色素浓缩激素（MCH）神经元的光遗传学激活增加了纹状体多巴胺水平，并逆转了对蔗糖与三氯蔗糖的正常偏好。相反，动物消融MCH神经元不再喜欢蔗糖三氯蔗糖，并显示减少纹状体DA释放蔗糖摄入后。我们进一步表明，MCH神经元投射到奖励区域，并且是甜盲Trpm 5 −/−小鼠中蔗糖摄入后奖励效应所必需的。这些研究确定了连接营养感测和食物奖励的神经通路的重要组成部分。http://dx.doi.org/10.7554/eLife.01462.001全糖碳酸饮料的销量几乎是减肥饮料的三倍，这为实验室发现的人类和动物更喜欢糖而不是人工甜味剂提供了现实世界的证实。然而，这不仅仅是因为含糖的东西味道更好。带有突变基因的小鼠无法感知甜味，但它们仍然更喜欢天然蔗糖，而不是人工甜味剂三氯蔗糖。这是因为糖与人造甜味剂不同，具有营养价值，人类和动物都发现食用高热量食物是有益的。众所周知，吃糖会导致大脑的某些部分释放更多的化学递质多巴胺，多巴胺用于发出奖励信号，但这一过程究竟如何产生对糖的偏好尚不清楚。现在，Domingos等人揭示了一个叫做下丘脑外侧的大脑区域负责这种效应。大脑的这一区域--帮助控制食欲，也与大脑的奖励系统相连--通常包含称为MCH神经元的细胞。Domingos等人表明，对蔗糖的天然偏好可以通过用光刺激MCH神经元来逆转，这反过来又刺激大脑中奖励中心的多巴胺释放。此外，与正常小鼠相比，外侧下丘脑中没有任何MCH神经元的突变小鼠对蔗糖的偏好降低，并且当它们消耗蔗糖时，它们释放的多巴胺比正常小鼠少。通过证明MCH神经元对于感知糖的营养价值既必要又足够，这些结果为糖渴望的生物学基础提供了新的见解。然而，考虑到过量食用糖对健康的影响，它们最终可能被用来寻找使糖不那么受欢迎的方法，或者使人造甜味剂更接近于模仿真实的东西。DOI：http://dx.doi.org/10.7554/eLife.01462.002网站
Sugars that contain glucose, such as sucrose, are generally preferred to artificial sweeteners owing to their post-ingestive rewarding effect, which elevates striatal dopamine (DA) release. While the post-ingestive rewarding effect, which artificial sweeteners do not have, signals the nutrient value of sugar and influences food preference, the neural circuitry that mediates the rewarding effect of glucose is unknown. In this study, we show that optogenetic activation of melanin-concentrating hormone (MCH) neurons during intake of the artificial sweetener sucralose increases striatal dopamine levels and inverts the normal preference for sucrose vs sucralose. Conversely, animals with ablation of MCH neurons no longer prefer sucrose to sucralose and show reduced striatal DA release upon sucrose ingestion. We further show that MCH neurons project to reward areas and are required for the post-ingestive rewarding effect of sucrose in sweet-blind Trpm5−/− mice. These studies identify an essential component of the neural pathways linking nutrient sensing and food reward. DOI: http://dx.doi.org/10.7554/eLife.01462.001 Sales of full-sugar fizzy drinks are almost triple those of diet versions, providing real-world confirmation of the laboratory finding that humans, as well as animals, prefer sugar to artificial sweeteners. However, it is not simply that sugary things taste better. Mice with a mutation that prevents them from perceiving sweet tastes still prefer the natural sugar sucrose over the artificial sweetener sucralose. This is because sugar, unlike artificial sweeteners, has nutritional value, and both humans and animals find it rewarding to consume foods with a high caloric content. Consuming sugar has been known to cause certain parts of the brain to release more of the chemical transmitter dopamine, which is used to signal reward, but exactly how this process produces a preference for sugar has been unclear. Now, Domingos et al. have revealed that a brain region called the lateral hypothalamus is responsible for this effect. This region of the brain—which helps to control appetite and which is also connected to the brain’s reward system—normally contains cells called MCH neurons. Domingos et al. show that the natural preference for sucrose over sucralose can be reversed by stimulating the MCH neurons with light, which in turn stimulates dopamine release in reward centers in the brain. Moreover, mutant mice that do not have any MCH neurons in the lateral hypothalamus show a reduced preference for sucrose over sucralose, compared to normal mice, and they release less dopamine than normal mice when they consume sucrose. By demonstrating that MCH neurons are both necessary and sufficient for sensing the nutritional value of sugar, these results provide new insights into the biological basis of sugar cravings. However, given the health implications of excessive sugar consumption, they may ultimately be used to find ways to make sugar less desirable, or to make artificial sweeteners more closely mimic the real thing. DOI: http://dx.doi.org/10.7554/eLife.01462.002