title: Histidine suppresses food intake through its conversion into neuronal histamine.
abstract: Hypothalamic neuronal histamine has been shown to regulate feeding behavior and energy metabolism as a target of leptin action in the brain. The present study aimed to examine the involvement of L-histidine, a precursor of neuronal histamine, in the regulation of feeding behavior in rats. Intraperitoneal (ip) injection of L-histidine at doses of 0.35 and 0.70 mmol/kg body weight significantly decreased the 24-hr cumulative food and water intakes compared to phosphate buffered saline injected controls (P < 0.05 for each). This suppression of feeding was mimicked dose-dependently by intracerebroventricular infusion of histidine at doses of 0.5, 1.0, and 2.0 micromol/rat (P < 0.05 for each). Pretreatment of the rats with an ip bolus injection of alpha-fluoromethylhistidine, a suicide inhibitor of a histidine decarboxylase (HDC), at a dosage of 224 micromol/kg blocked the conversion of histidine into histamine and attenuated the suppressive effect of histidine on food intake from 64.2% to 88.1% of the controls (P < 0.05). Administration of 0.35 mmol/kg histidine ip increased the concentration of hypothalamic neuronal histamine compared with the controls (P < 0.05). HDC activity was increased simultaneously by histidine administration compared with the controls (P < 0.05). The present findings indicate that L-histidine suppresses food intake through its conversion into histamine in the hypothalamus.
authors.affiliation: Department of Internal Medicine I, School of Medicine, Oita Medical University, Hasama, Oita, 879-5593, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yoshimatsu
authors.forename: Seiichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tajima
authors.forename: Yuko
authors.initials: Y
authors.lastname: Akehi
authors.forename: Toshiie
authors.initials: T
authors.lastname: Sakata
mesh_terms: D000818:Animals; D004435:Eating / Q000187:drug effects* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism*; D006639:Histidine / Q000494:pharmacology*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D008762:Methylhistidines; D006639:Histidine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase