Neuronal histamine regulates food intake, adiposity, and uncoupling protein expression in agouti yellow (A(y)/a) obese mice.
Hypothalamic neuronal histamine and its H(1) receptor (H(1)-R) form a part of the leptin-signaling pathway in the brain and have been shown to regulate body weight and adiposity in diabetic (db/db) and diet-induced obese mice by affecting food intake and uncoupling protein mRNA expression. The proopiomelanocortin (POMC) melanocortin-4 receptor (MC-4R) is also important for leptin signaling. The present study had two aims: first, to clarify the antiobesity action of neuronal histamine in agouti yellow (A(y)/a) obese mice, a model of obesity in which POMC/MC-4R signaling is disrupted by blockade of MC-4R and second, to investigate the functional relationship between neuronal histamine and POMC/MC-4R signaling. Central administration of histamine into the lateral cerebroventricle decreased cumulative food intake and body weight in A(y)/a obese mice. Histamine treatment also decreased mRNA expression of ob gene in epididymal white adipose tissue and up-regulated uncoupling protein 1 mRNA expression in brown adipose tissue. These effects were attenuated in A(y)/a obese mice with histamine H(1)-receptor (H(1)-R) knockout. Histamine treatment induced c-Fos-like immunoreactivity in both paraventricular and arcuate nucleus. There was no significant difference in histamine-induced c-Fos-like immunoreactivity in the hypothalamus between A(y)/a obese mice and lean littermates, indicating histamine signaling was not disrupted at the hypothalamic level in A(y)/a obese mice. These results suggest that neuronal histamine have an antiobese action, even in A(y)/a obese mice despite a deficiency in POMC/MC-4R signaling. In addition, it appears that the histamine H(1)-R signaling pathway may be independent or downstream of the POMC/MC-4R signaling.
Department of Internal Medicine, School of Medicine, Oita Medical University, Oita 879-5593, Japan. masaki@oita-med.ac.jp
Takayuki
T
Masaki
Seiichi
S
Chiba
Go
G
Yoshimichi
Tohru
T
Yasuda
Hitoshi
H
Noguchi
Tetsuya
T
Kakuma
Toshiie
T
Sakata
Hironobu
H
Yoshimatsu
D002001:Adipose Tissue, Brown / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics*; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006632:Histamine / Q000494:pharmacology*; D007031:Hypothalamus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D007276:Injections, Intraventricular; D007473:Ion Channels; D020738:Leptin / Q000097:blood / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D024101:Mitochondrial Proteins; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D011969:Receptors, Histamine H1 / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D014280:Triglycerides / Q000097:blood; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D014280:Triglycerides; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D011333:Pro-Opiomelanocortin; D006632:Histamine