Transient receptor potential vanilloid 1 (TRPV1), a nociceptive cation channel, is known to play roles in regulating the energy metabolism (EM) of the whole body. We previously reported that TRPV1 antagonists such as AMG517 enhanced EM in mice, however, these mechanisms remain unclear. The aim of this study was to explore the mechanisms underlying the enhancement of EM by AMG517, a selective TRPV1 antagonist, in mice. Respiratory gas analysis indicated that intragastric administration of AMG517 enhanced EM along with increasing locomotor activity in mice. Next, to clarify the possible involvement with afferent sensory nerves, including the vagus, we desensitized the capsaicin-sensitive sensory nerves of mice by systemic capsaicin treatment. In the desensitized mice, intragastric administration of AMG517 did not change EM and locomotor activity. Therefore, this study indicated that intragastric administration of AMG517 enhanced EM and increased locomotor activity via capsaicin-sensitive sensory nerves, including vagal afferents in mice.

瞬态受体电位香草酸1（TRPV1）是一种伤害性阳离子通道，已知在调节全身的能量代谢（EM）中发挥作用。我们先前曾报道TRPV1拮抗剂（例如AMG517）在小鼠中增强了EM，但是，这些机制仍不清楚。这项研究的目的是探索小鼠选择性TRPV1拮抗剂AMG517增强EM的潜在机制。呼吸气体分析表明，AMG517的胃内给药可增强小鼠的EM以及运动能力。接下来，为了阐明可能涉及传入神经包括迷走神经，我们通过全身辣椒素治疗使小鼠对辣椒素敏感的感觉神经不敏感。在脱敏小鼠中，AMG517的胃内给药不会改变EM和运动功能。通过辣椒素敏感的感觉神经，包括小鼠的迷走神经传入。