Neuropeptide W: an anorectic peptide regulated by leptin and metabolic state.
Neuropeptide W (NPW) is an anorectic peptide produced in the brain. Here, we showed that NPW was present in several hypothalamic nuclei, including the paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, lateral hypothalamus, and hypothalamic arcuate nucleus. NPW expression was significantly up-regulated in leptin-deficient ob/ob and leptin receptor-deficient db/db mice. The increase in NPW expression in ob/ob mice was abrogated to control levels after leptin replacement. Leptin induced suppressors of cytokine signaling-3 after phosphorylation of signal transducer and activator of transcription-3 in NPW-expressing neurons. In addition, we demonstrated that NPW reduces feeding via the melanocortin-4-receptor signaling pathway. We also showed that NPW activates proopiomelanocortin and inhibits neuropeptide Y neurons using loose-patch extracellular recording of these neurons identified by promoter-driven green fluorescent protein expression. This study indicates that NPW may play an important role in the regulation of feeding and energy metabolism under the conditions of leptin insufficiency.
Date
Yukari
Y
Frontier Science Research Center, University of Miyazaki, Kiyotake, Miyazaki, Japan.
Mondal
Muhtashan S
MS
Kageyama
Haruaki
H
Ghamari-Langroudi
Masoud
M
Takenoya
Fumiko
F
Yamaguchi
Hideki
H
Shimomura
Yukio
Y
Mori
Masaaki
M
Murakami
Noboru
N
Shioda
Seiji
S
Cone
Roger D
RD
Nakazato
Masamitsu
M
D000818:Animals; D000855:Anorexia / Q000378:metabolism; D001481:Basal Metabolism / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D020738:Leptin / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D020738:Leptin; D009478:Neuropeptide Y; D009479:Neuropeptides; D044105:Receptor, Melanocortin, Type 4; D050796:STAT3 Transcription Factor; C508547:neuropeptide W, mouse