Endocannabinoids selectively enhance sweet taste
Endocannabinoids selectively enhance sweet taste
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DOI：
10.1073/pnas.0912048107
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发表时间：
2010-01-12
影响因子：
11.1
通讯作者：
Ninomiya, Yuzo
中科院分区：
文献类型：
--
作者：
Yoshida, Ryusuke;Ohkuri, Tadahiro;Ninomiya, Yuzo
内源性大麻素如花生四烯酸乙醇胺[N-花生四烯酸乙醇胺（AEA）]和2-花生四烯酸甘油（2-AG）是已知的促食欲介质，其通过下丘脑和边缘前脑中的CB 1受体起作用以诱导食欲并刺激食物摄入。循环内源性大麻素水平与血浆瘦素水平呈负相关，瘦素是一种通过作用于下丘脑受体来减少食物摄入的致癌介质。最近，味觉被发现是瘦素的外周靶点。瘦素选择性抑制甜味反应在野生型小鼠，但不是在瘦素受体缺陷型db/db小鼠。在这里，我们表明，内源性大麻素反对瘦素作为甜味增强剂的作用。我们发现，AEA或2-AG的管理增加味觉神经反应的甜味剂在浓度依赖性的方式，而不影响响应咸，酸，苦，和鲜味化合物。大麻素增加对甜-苦混合物的行为反应和味觉感受器细胞对甜味化合物的电生理反应。遗传上缺乏CB 1受体的小鼠在细胞、神经或行为水平上没有表现出内cannabinoids对甜味反应的增强作用。此外，内源性大麻素对味觉细胞甜味反应的影响被CB 1受体拮抗剂AM 251减弱，但不被CB 2受体拮抗剂AM 630减弱。免疫组织化学显示，CB 1受体表达在II型味觉细胞，也表达T1 r3甜味受体成分。总之，这些观察结果表明，味觉器官是内源性大麻素的外周靶点。内源性大麻素和瘦素对外周甜味的相互调节可能有助于它们对食物摄入的相反作用，并在调节能量稳态中发挥重要作用。
Endocannabinoids such as anandamide [N-arachidonoylethanolamine (AEA)] and 2-arachidonoyl glycerol (2-AG) are known orexigenic mediators that act via CB1 receptors in hypothalamus and limbic forebrain to induce appetite and stimulate food intake. Circulating endocannabinoid levels inversely correlate with plasma levels of leptin, an anorexigenic mediator that reduces food intake by acting on hypothalamic receptors. Recently, taste has been found to be a peripheral target of leptin. Leptin selectively suppresses sweet taste responses in wild-type mice but not in leptin receptor-deficient db/db mice. Here, we show that endocannabinoids oppose the action of leptin to act as enhancers of sweet taste. We found that administration of AEA or 2-AG increases gustatory nerve responses to sweeteners in a concentration-dependent manner without affecting responses to salty, sour, bitter, and umami compounds. The cannabinoids increase behavioral responses to sweet-bitter mixtures and electrophysiological responses of taste receptor cells to sweet compounds. Mice genetically lacking CB1 receptors show no enhancement by endocannnabinoids of sweet taste responses at cellular, nerve, or behavioral levels. In addition, the effects of endocannabinoids on sweet taste responses of taste cells are diminished by AM251, a CB1 receptor antagonist, but not by AM630, a CB2 receptor antagonist. Immunohistochemistry shows that CB1 receptors are expressed in type II taste cells that also express the T1r3 sweet taste receptor component. Taken together, these observations suggest that the taste organ is a peripheral target of endocannabinoids. Reciprocal regulation of peripheral sweet taste reception by endocannabinoids and leptin may contribute to their opposing actions on food intake and play an important role in regulating energy homeostasis.