Transient receptor potential vanilloid 1 (TRPV1) is a nociceptive cation channel that is activated by heat, protons and chemical ligands such as capsaicin. We investigated the roles of the capsaicin receptor, TRPV1, in controlling the energy metabolism of the whole body. It has been reported that the activation of TRPV1 by its agonists enhances energy metabolism. In this study, we used a respiratory gas analysis system to examine whether the inhibition of TRPV1 changes energy metabolism in mice. In addition, we examined the contributions of different modes of TRPV1 activation (heat, protons and capsaicin) to determine the influence of 3 different TRPV1 antagonists on energy metabolism. Here, we showed that intragastric administration of AMG517, a nonselective antagonist of TRPV1 (for heat, protons and capsaicin), enhanced energy metabolism as much as did intraperitoneal administration. On the other hand, intraperitoneal administration of AMG9810, a nonselective antagonist like AMG517, enhanced energy expenditure more than intragastric administration. However, the administration of JYL1421, a TRPV1 antagonist that very strongly inhibits TRPV1 activated by capsaicin, did not change energy metabolism. Taken together, these results suggest that the type of TRPV1 antagonists and the routes of its administration have different effects on energy metabolism in a normal body. Surprisingly, co-administration of JYL1421 and capsaicin significantly enhanced the energy metabolism more than administration of capsaicin alone. These results support the possibility that an unconventional mechanism is responsible for the increase in energy metabolism that occurs via TRPV1 inhibition.

中文翻译：

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TRPV1拮抗剂对小鼠能量代谢的作用差异。

瞬态受体电位香草酸1（TRPV1）是一种伤害性阳离子通道，可被热量，质子和辣椒素等化学配体激活。我们研究了辣椒素受体TRPV1在控制全身能量代谢中的作用。据报道，其激动剂激活TRPV1可增强能量代谢。在这项研究中，我们使用了呼吸气体分析系统来检查TRPV1的抑制作用是否会改变小鼠的能量代谢。此外，我们检查了TRPV1激活不同模式（热，质子和辣椒素）的贡献，以确定3种不同的TRPV1拮抗剂对能量代谢的影响。在这里，我们证明了胃内施用AMG517（TRPV1的非选择性拮抗剂）（用于加热，质子和辣椒素），腹膜内给药可以增强能量代谢。另一方面，腹膜内给予AMG9810（一种非选择性拮抗剂，如AMG517）比胃内给予的能量消耗更多。但是，非常强烈地抑制辣椒素激活的TRPV1的TRPV1拮抗剂JYL1421的给药并没有改变能量代谢。综上所述，这些结果表明TRPV1拮抗剂的类型及其给药途径对正常人体能量代谢的影响不同。令人惊讶的是，与单独施用辣椒素相比，JYL1421和辣椒素的共同施用显着增强了能量代谢。