Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus.
Ghrelin, a gastrointestinal peptide, stimulates feeding when administered peripherally. Blockade of the vagal afferent pathway abolishes ghrelin-induced feeding, indicating that the vagal afferent pathway may be a route conveying orexigenic ghrelin signals to the brain. Here, we demonstrate that peripheral ghrelin signaling, which travels to the nucleus tractus solitarius (NTS) at least in part via the vagus nerve, increases noradrenaline (NA) in the arcuate nucleus of the hypothalamus, thereby stimulating feeding at least partially through alpha-1 and beta-2 noradrenergic receptors. In addition, bilateral midbrain transections rostral to the NTS, or toxin-induced loss of neurons in the hindbrain that express dopamine beta hydroxylase (an NA synthetic enzyme), abolished ghrelin-induced feeding. These findings provide new evidence that the noradrenergic system is necessary in the central control of feeding behavior by peripherally administered ghrelin.
Date
Yukari
Y
Third Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Miyazaki 889-1692, Japan. dateyuka@med.miyazaki-u.ac.jp
Shimbara
Takuya
T
Koda
Shuichi
S
Toshinai
Koji
K
Ida
Takanori
T
Murakami
Noboru
N
Miyazato
Mikiya
M
Kokame
Koichi
K
Ishizuka
Yuta
Y
Ishida
Yasushi
Y
Kageyama
Haruaki
H
Shioda
Seiji
S
Kangawa
Kenji
K
Nakazato
Masamitsu
M
D000818:Animals; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D054439:Ghrelin; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D036361:Peptide Hormones / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D012249:Rhombencephalon / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D054439:Ghrelin; D009478:Neuropeptide Y; D036361:Peptide Hormones; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D018343:Receptors, Adrenergic, beta-2; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine