Nesfatin‐1, corticotropin‐releasing hormone, thyrotropin‐releasing hormone, and neuronal histamine interact in the hypothalamus to regulate feeding behavior

• Published in: Journal of neurochemistry 2013-01, Vol.124 (1), p.90-99
• Main Authors: Gotoh, Koro, Masaki, Takayuki, Chiba, Seiichi, Ando, Hisae, Shimasaki, Takanobu, Mitsutomi, Kimihiko, Fujiwara, Kansuke, Katsuragi, Isao, Kakuma, Tetsuya, Sakata, Toshiie, Yoshimatsu, Hironobu
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Brain research; Calcium-Binding Proteins - blood; Calcium-Binding Proteins - pharmacology; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - administration & dosage; Corticotropin-Releasing Hormone - metabolism; CRH; DNA-Binding Proteins - blood; DNA-Binding Proteins - pharmacology; Eating - genetics; Eating - physiology; Feeding behavior; Feeding Behavior - physiology; Food intake; Histamine; Histamine - metabolism; Histamine - pharmacology; Histamine H1 receptors; Histidine; Histidine decarboxylase; Hormones; Hypothalamus; Hypothalamus - cytology; Hypothalamus - drug effects; Hypothalamus - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins - blood; Nerve Tissue Proteins - pharmacology; nesfatin‐1; Neurobiology; Neurons; Neurons - drug effects; Neurons - metabolism; Paraventricular nucleus; Rats; Rats, Sprague-Dawley; Receptors, Histamine H1 - deficiency; Suicide; Thyrotropin-releasing hormone; Thyrotropin-Releasing Hormone - metabolism; Thyrotropin-Releasing Hormone - pharmacology; TRH
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.12066

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. Nesfatin‐1, corticotropin‐releasing hormone (CRH), thyrotropin‐releasing hormone (TRH) and hypothalamic neuronal histamine act as anorexigenics in the hypothalamus. Nesfatin‐1 increased CRH and TRH levels and histamine turnover, whereas histamine also increased nesfatin‐1 level in the hypothalamus. These results indicate that CRH, TRH and hypothalamic neuronal histamine mediate the suppressive effects of nesfatin‐1 on feeding behavior.