title: Nesfatin-1, corticotropin-releasing hormone, thyrotropin-releasing hormone, and neuronal histamine interact in the hypothalamus to regulate feeding behavior.
abstract: Nesfatin-1, corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and hypothalamic neuronal histamine act as anorexigenics in the hypothalamus. We examined interactions among nesfatin-1, CRH, TRH, and histamine in the regulation of feeding behavior in rodents. We investigated whether the anorectic effect of nesfatin-1, α-fluoromethyl histidine (FMH; a specific suicide inhibitor of histidine decarboxylase that depletes hypothalamic neuronal histamine), a CRH antagonist, or anti-TRH antibody affects the anorectic effect of nesfatin-1, whether nesfatin-1 increases CRH and TRH contents and histamine turnover in the hypothalamus, and whether histamine increases nesfatin-1 content in the hypothalamus. We also investigated whether nesfatin-1 decreases food intake in mice with targeted disruption of the histamine H1 receptor (H1KO mice) and if the H1 receptor (H1-R) co-localizes in nesfatin-1 neurons. Nesfatin-1-suppressed feeding was partially attenuated in rats administered with FMH, a CRH antagonist, or anti-TRH antibody, and in H1KO mice. Nesfatin-1 increased CRH and TRH levels and histamine turnover, whereas histamine increased nesfatin-1 in the hypothalamus. Immunohistochemical analysis revealed H1-R expression on nesfatin-1 neurons in the paraventricular nucleus of the hypothalamus. These results indicate that CRH, TRH, and hypothalamic neuronal histamine mediate the suppressive effects of nesfatin-1 on feeding behavior.
authors.affiliation: Department of Internal Medicine 1, Faculty of Medicine, Oita University, Yufu, Japan. gotokoro@oita-u.ac.jp
authors.forename: Koro
authors.initials: K
authors.lastname: Gotoh
authors.forename: Takayuki
authors.initials: T
authors.lastname: Masaki
authors.forename: Seiichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Hisae
authors.initials: H
authors.lastname: Ando
authors.forename: Takanobu
authors.initials: T
authors.lastname: Shimasaki
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Mitsutomi
authors.forename: Kansuke
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Isao
authors.initials: I
authors.lastname: Katsuragi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kakuma
authors.forename: Toshiie
authors.initials: T
authors.lastname: Sakata
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yoshimatsu
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000097:blood* / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000097:blood* / Q000494:pharmacology; D004435:Eating / Q000235:genetics / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D006632:Histamine / Q000378:metabolism* / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000097:blood* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D000080866:Nucleobindins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011969:Receptors, Histamine H1 / Q000172:deficiency; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D011969:Receptors, Histamine H1; D013973:Thyrotropin-Releasing Hormone; D006632:Histamine; D003346:Corticotropin-Releasing Hormone