保守的内源性大麻素大麻素酰胺调节嗅觉敏感性,诱导线虫的享乐性进食。
The conserved endocannabinoid anandamide modulates olfactory sensitivity to induce hedonic feeding in C. elegans.
机构信息
University of Oregon, Institute of Neuroscience, 1245 University of Oregon, Eugene, OR 97403, USA.
University of Oregon, Institute of Neuroscience, 1245 University of Oregon, Eugene, OR 97403, USA.
出版信息
Curr Biol. 2023 May 8;33(9):1625-1639.e4. doi: 10.1016/j.cub.2023.03.013. Epub 2023 Apr 20.
The ability of cannabis to increase food consumption has been known for centuries. In addition to producing hyperphagia, cannabinoids can amplify existing preferences for calorically dense, palatable food sources, a phenomenon called hedonic amplification of feeding. These effects result from the action of plant-derived cannabinoids that mimic endogenous ligands called endocannabinoids. The high degree of conservation of cannabinoid signaling at the molecular level across the animal kingdom suggests hedonic feeding may also be widely conserved. Here, we show that exposure of Caenorhabditis elegans to anandamide, an endocannabinoid common to nematodes and mammals, shifts both appetitive and consummatory responses toward nutritionally superior food, an effect analogous to hedonic feeding. We find that anandamide's effect on feeding requires the C. elegans cannabinoid receptor NPR-19 but can also be mediated by the human CB1 cannabinoid receptor, indicating functional conservation between the nematode and mammalian endocannabinoid systems for the regulation of food preferences. Furthermore, anandamide has reciprocal effects on appetitive and consummatory responses to food, increasing and decreasing responses to inferior and superior foods, respectively. Anandamide's behavioral effects require the AWC chemosensory neurons, and anandamide renders these neurons more sensitive to superior foods and less sensitive to inferior foods, mirroring the reciprocal effects seen at the behavioral level. Our findings reveal a surprising degree of functional conservation in the effects of endocannabinoids on hedonic feeding across species and establish a new system to investigate the cellular and molecular basis of endocannabinoid system function in the regulation of food choice.
大麻增加食物消耗的能力已为人所知数百年。除了产生多食症外,大麻素还可以放大对高热量、美味食物的现有偏好,这种现象被称为进食愉悦放大。这些效应是由植物衍生的大麻素引起的,这些大麻素模拟内源性配体,称为内源性大麻素。在动物王国中,大麻素信号在分子水平上高度保守,这表明愉悦进食可能也广泛保守。在这里,我们表明,暴露于线虫和哺乳动物共有的内源性大麻素——花生四烯酰乙醇胺,会使秀丽隐杆线虫的食欲和摄食反应向营养更优的食物转移,这一效应类似于进食愉悦。我们发现,花生四烯酰乙醇胺对摄食的影响需要秀丽隐杆线虫的大麻素受体 NPR-19,但也可以被人类 CB1 大麻素受体介导,表明线虫和哺乳动物内源性大麻素系统在调节食物偏好方面具有功能保守性。此外,花生四烯酰乙醇胺对食物的食欲和摄食反应都有相互的影响,分别增加和减少对劣质和优质食物的反应。花生四烯酰乙醇胺的行为效应需要 AWC 化学感觉神经元,而花生四烯酰乙醇胺使这些神经元对优质食物更敏感,对劣质食物更不敏感,这反映了在行为水平上观察到的相互作用。我们的发现揭示了内源性大麻素在跨物种的进食愉悦中的作用具有惊人的功能保守性,并建立了一个新的系统来研究内源性大麻素系统在调节食物选择中的细胞和分子基础。
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