Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menopause is one of the triggers that induce obesity. Estradiol (E2), corticotropin-releasing hormone (CRH), and hypothalamic neuronal histamine are anorexigenic substances within the hypothalamus. This study examined the interactions among E2, CRH, and histamine during the regulation of feeding behavior and obesity in rodents. Food intake was measured in rats after the treatment of E2, alpha-fluoromethyl histidine, a specific suicide inhibitor of histidine decarboxylase that depletes hypothalamic neuronal histamine, or CRH antagonist. We measured food intake and body weight in wild-type mice or mice with targeted disruption of the histamine receptors (H1-R) knockout (H1KO mice). Furthermore, we investigated CRH content and histamine turnover in the hypothalamus after the E2 treatment or ovariectomy (OVX). We used immunohistochemical staining for estrogen receptors (ERs) in the histamine neurons. The E2-induced suppression of feeding was partially attenuated in rats pre-treated with alpha-fluoromethyl histidine or CRH antagonist and in H1KO mice. E2 treatment increased CRH content and histamine turnover in the hypothalamus. OVX increased food intake and body weight, and decreased CRH content and histamine turnover in the hypothalamus. In addition, E2 replacement reversed the OVX-induced changes in food intake and body weight in wild-type mice but not in H1KO mice. Immunohistochemical analysis revealed ERs were expressed on histamine neurons and western blotting analysis and pre-absorption study confirmed the specificity of ER antiserum we used. These results indicate that CRH and hypothalamic neuronal histamine mediate the suppressive effects of E2 on feeding behavior and body weight.
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PMID:Hypothalamic neuronal histamine signaling in the estrogen deficiency-induced obesity. 1961 43

Obesity is the effect of imbalance between energy intake and expenditure and forms a fundamental basis of the metabolic syndrome. A number of substances implicated in the regulation of energy metabolism represent opportunities for anti-obesity drug development. Neuronal histamine and its receptors have been shown to regulate energy metabolism and are considered as anti-obesity targets. Several histamine receptor subtypes have been identified; of these, histamine H1 and H3 receptors (H1-R and H3-R) have been specifically recognized as mediators of energy intake and expenditure. In addition, several histamine drugs related to H1-R and H3-R, have been shown to attenuate body weight gain both in rodent and human. These results provide the reagents for histamine receptors biology and may find applications in the treatment of obesity and related metabolic disorders. In this review, the development of agonists and antagonists of histamine receptors are provided.
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PMID:Neuronal histamine and its receptors: implication of the pharmacological treatment of obesity. 2106 48