Analysis of peripheral ghrelin signaling via the vagus nerve in ghrelin receptor–restored GHSR-null mice

•GHSR/Phox2b mice express GHSR specifically in the vagus nerve.•Restoration of GHSR in the nodose ganglion is sufficient to regulate blood glucose.•GHSR expression in the vagus nerve is critical for peripheral ghrelin signaling.•GHSR expression in the vagus nerve influences circadian fluctuations in feeding. The vagus nerve connects peripheral organs to the central nervous system (CNS), and gastrointestinal hormones transmit their signals to the CNS via the vagal afferent nerve. Ghrelin, a gastric-derived orexigenic peptide, stimulates food intake by transmitting starvation signals via the vagus nerve. To understand peripheral ghrelin signaling via the vagus nerve, we investigated the ghrelin receptor (GHSR)-null mouse. For this purpose, we tried to produce mice in which GHSR was selectively expressed in the hindbrain and vagus nerve. GHSR was expressed in some nodose ganglion neurons in these mice, but GHSR-expressing neurons were less abundant than in wild-type mice. Intraperitoneal administration of ghrelin did not induce food intake or growth hormone release, but did increase blood glucose levels. Our findings suggest that the abundance of GHSR-expressing neurons in the nodose ganglion is critical for peripheral administration of ghrelin-induced food intake and growth hormone release via the vagus nerve.