Central actions of neuromedin U via corticotropin-releasing hormone.
Neuromedin U (NMU), a hypothalamic peptide, has been known to be involved in feeding behavior as a catabolic signaling molecule. However, little is known about the participation of NMU in the neuronal network. One NMU receptor, NMU2R, is abundantly expressed in the hypothalamic paraventricular nucleus, where corticotrophin-releasing hormone (CRH) is synthesized. The functions of CRH, regulation of stress response and feeding behavior, are comparable with those of NMU. Here, we have investigated the functional relationships between NMU and CRH using CRH knockout (KO) mice. Intracerebroventricular administration of NMU suppressed dark-phase food intake and fasting-induced feeding in wild-type mice. In contrast, these suppressions were not observed in CRH KO mice. NMU-induced increases in oxygen consumption and body temperature were attenuated in CRH KO mice. These results suggest that NMU plays a role in feeding behavior and catabolic functions via CRH. This study demonstrates a novel hypothalamic pathway that links NMU and CRH in the regulation of feeding behavior and energy homeostasis.
Hanada
Takeshi
T
Third Department of Internal Medicine, Miyazaki Medical College, 889-1692, Miyazaki, Japan.
Date
Yukari
Y
Shimbara
Takuya
T
Sakihara
Satoru
S
Murakami
Noboru
N
Hayashi
Yujiro
Y
Kanai
Yasushi
Y
Suda
Toshihiro
T
Kangawa
Kenji
K
Nakazato
Masamitsu
M
D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000172:deficiency / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000008:administration & dosage*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology
D009479:Neuropeptides; C056900:neuromedin U; D003346:Corticotropin-Releasing Hormone