A-967079

Pro-opiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) play a pivotal role in regulating brown adipose tissue (BAT) thermogenesis via the sympathetic nervous system. The activation of transient receptor potential ankyrin 1 (TRPA1) has been demonstrated to enhance heat production, particularly in BAT. However, no direct evidence has been reported regarding BAT thermogenesis mediated by TRPA1-regulated ARC POMC neurons. This study aimed to investigate the role of TRPA1-expressing hypothalamic POMC neurons in BAT thermogenesis. To confirm TRPA1 expression in ARC POMC neurons, we employed single-cell reverse transcriptase polymerase chain reaction and immunolabeling techniques. Selective TRPA1 agonists, including capsiate and ASP7663, induced depolarization of ARC POMC neurons, an effect that was inhibited by A967079, a TRPA1-selective antagonist. Furthermore, intracerebroventricular (i.c.v.) administration of ASP7663 increased BAT and core body temperature. The thermogenic effect of ASP7663 in BAT was abolished by co-administration of A967079. Among the BAT thermogenic markers, peroxisome proliferator-activated receptor gamma coactivator 1-alpha and PR domain containing 16 (PRDM16) expressions were considerably upregulated following i.c.v. administration of ASP7663. However, this increase was reversed by A967079, except for PRDM16. These findings indicate that TRPA1-mediated activation of hypothalamic POMC neurons is critical in regulating BAT thermogenesis and promoting energy expenditure.