SPLTRAK Abstract Submission
The Mechanisms of the Enhancement of Energy Metabolism by AMG517, a TRPV1 Antagonist in Mice
Jun Hai1, Fuminori Kawabata2, Yuko Kawabata3, Shotaro Nishimura1, Shoji Tabata1
1Laboratory of Functional Anatomy, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
2Physiology of Domestic Animals, Faculty of Agriculture and Life Science, Hirosaki, Japan
3Section of Oral Neuroscience, Graduate School of Dental Sciences, Fukuoka, Japan

Transient receptor potential vanilloid 1 (TRPV1) is a nociceptive cation channel activated by heat, protons and chemical ligands such as capsaicin.  We have investigated the roles of TRPV1 in the modulation of energy metabolism in vivo.  Although, it has been reported that the activation of TRPV1 by its agonists enhances energy metabolism, we previously revealed that the inhibition of TRPV1 by its antagonists also enhanced energy metabolism in mice.  However, its mechanisms remain unclear.  The aim of this study is to explore the mechanisms underlying the enhancement of energy metabolism by TRPV1 antagonist in mice.  We used AMG517 as TRPV1 antagonist.  Both oral and intraperitoneal administrations of AMG517 enhanced energy metabolism.  In the mice desensitized to afferent sensory nerves expressing TRPV1 by pretreatment of capsaicin, oral administration of AMG517 did not change energy metabolism.  Next, to clarify the involvement with the sympathetic nervous system, we investigated the effect of propranolol, a β-adrenoceptor antagonist, on the enhancement of energy metabolism by AMG517.  Pretreatment of propranolol partially suppressed the enhancement of energy metabolism by oral administration of AMG517.  On the other hand, pretreatment of propranolol almost abolished the enhancement of energy metabolism and locomotor activity level by intraperitoneal administration of AMG517.  These results suggested that oral administration of TRPV1 antagonist enhanced energy metabolism via afferent sensory nerves including vagal nerves, and intraperitoneal administration of TRPV1 antagonist enhanced energy metabolism by increasing the sympathetic nerve activity and the locomotor activity in mice.