Host: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
Name : WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
Location : Kyoto
Date : July 01, 2018 - July 06, 2018
Brown adipose tissue (BAT) is one of the major site for mammalian non-shivering thermogenesis. While, thermogenesis is thought to be occurred by the activation of UCP1 in the downstream of 3 adrenergic receptor activation, its mechanisms have not been well established. Especially, it has not been reported whether Ca2+ signaling works during thermogenesis. To clarify this, we focused on transient receptor potential vanilloid 2 (TRPV2) which is a Ca2+-permeable non-selective cation channel, and analyzed TRPV2 knockout (TRPV2KO) mice. mRNA levels of thermogenic genes were significantly lower in brown adipose tissue (BAT) from TRPV2KO mice and the size of lipid droplets and brown adipocytes was significantly larger in BAT from TRPV2KO mice. In addition, TRPV2KO mice showed cold intolerance and less increases in BAT temperature to beta-adrenergic receptor stimulation in vivo. Increases in the genes related to thermogenesis by beta-adrenergic receptor agonist or adenylate cyclase activator were significantly impaired in TRPV2KO brown adipocytes. In wild-type brown adipocytes, increases in the genes related to thermogenesis were suppressed by chelation of intracellular Ca2+. Based on these findings, we concluded that activation of TRPV2 in the downstream of beta-adrenergic receptor activation can cause thermogenesis in BAT and TRPV2 could be a drug target for human obesity.
