Neuronal histamine in the hypothalamus suppresses food intake in rats

Ookuma, Kazuyoshi; Sakata, Toshiie; Fukagawa, Koji; Yoshimatsu, Hironobu; Kurokawa, Mamoru; Machidori, Hironobu; Fujimoto, Kazuma

doi:10.1016/0006-8993(93)90960-u

Cited by 117 publications

(81 citation statements)

References 34 publications

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“…Intracerebroventricular administration of this compound significantly increases food intake in rats. [16][17][18][19] Together, these findings provide consistent evidence for histamine being an anorexigenic agent.…”

Section: Introductionsupporting

confidence: 60%

Effect of histaminergic manipulation on weight in obese adults: a randomized placebo controlled trial

Barak¹,

Greenway

Fujioka

et al. 2008

Int J Obes

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Objective: To determine the magnitude and determinants of weight loss in humans exposed to betahistine, a centrally acting histamine-1 (H-1) agonist and partial histamine-3 (H-3) antagonist. Design: A multicenter randomized, placebo-controlled dose-ranging weight loss trial with a 12-week treatment period. Subjects: Two hundred and eighty-one obese but otherwise healthy participants. Measurements: Weight and obesity-related comorbidities at baseline and at the end of the intervention. Results: Betahistine, at the doses tested, did not induce significant weight loss. With the exception of headache, no difference in adverse effect profile was noted between placebo and treatment groups. Subgroup analysis revealed that age below 50 years, ethnicity (non-Hispanics) and gender (women) were the strongest predictors of weight loss in this population. When these three factors were combined together, the betahistine 48 mg group (n ¼ 23) lost À4.24 ± 3.87 kg, whereas the placebo group (n ¼ 25) lost À1.65±2.96 kg during this time period (P ¼ 0.005). Conclusion: Betahistine, at the doses tested, induced significant weight loss with minimal adverse events only in women below 50 years.

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Section: Introductionsupporting

confidence: 60%

Effect of histaminergic manipulation on weight in obese adults: a randomized placebo controlled trial

Barak¹,

Greenway

Fujioka

et al. 2008

Int J Obes

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“…Brain histamine appears to suppress food intake via histamine H1 receptors. Centrally administered histamine H1 receptor agonists suppressed food consumption in rats (Lecklin et al, 1998), whereas injection of H1-antagonists elicited food intake (Sakata et al, 1988;Ookuma et al, 1993). However, relatively few studies have been carried out to unequivocally establish a relationship between food consumption and H1 receptors blockade in humans (Deng et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Pleiotropic effect of histamine H4 receptor modulation in the central nervous system

2013

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a b s t r a c tThe histamine H4 receptor (H4R) is expressed primarily on cells involved in inflammation and immune responses. Recently, it has been reported the functional expression of H4R within neurons of the central nervous system, but their role has been poorly understood. The present study aimed to elucidate the physiopathological role of cerebral H4R in animal models by the intracerebroventricular administration of the H4R agonist VUF 8430 (20e40 mg per mouse). Selectivity of results was confirmed by the prevention of the effects produced by the H4R antagonist JNJ 10191584 (3e9 mg/kg p.o.). Neuronal H4R activation induced acute thermal antinociception, indicating that neuronal histamine H4R might be involved in the production of antinociception in the absence of an inflammatory process. An anxiolyticlike effect of intensity comparable to that exerted by diazepam, used as reference drug, was produced in the lightedark box test. VUF 8430 reversed the scopolamine-induced amnesia in the passive avoidance test and showed anorexant activity in food deprived mice. Conversely, the H4R activation did not modify the immobility time in the tail suspension test. Rotarod performance test was employed to demonstrate that the effects observed following the administration of VUF 8430 and JNJ 10191584 were not due to impaired motor function of animals. Furthermore, both compounds did not alter spontaneous mobility and exploratory activity in the hole board test. These results show the antinociceptive, antiamnesic, anxiolytic and anorexant effects induced by neuronal H4R agonism, suggesting that H4 modulators may have broader utility further the control of inflammatory and immune processes.

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“…Elevation of histamine levels in the brain, by either direct administration of histamine or systemic administration of its precursor, histidine, results in appetite suppression, and a number of pharmacological studies have suggested the involvement of H1 receptors (5,8,13,(15)(16)(17)(18). This finding was confirmed by this study, which shows that inhibition of histamine release by ␣-FMH increased appetite slightly at 4 h and significantly at 12 h. In contrast, comparable inhibition of histamine release by imetit resulted in appetite suppression, suggesting that imetit decreases appetite independently of histaminergic tone modulation.…”

Section: Discussionmentioning

confidence: 99%

“…However, enhanced histamine release was accompanied by obese and hyperphagia phenotypes in H3RKO mice. Moreover, the effects of pharmacological blockade of H3Rs on appetite and energy homeostasis have remained controversial (6,13,(15)(16)(17)(18)(19).…”

mentioning

confidence: 99%

Therapeutic potential of histamine H3 receptor agonist for the treatment of obesity and diabetes mellitus

Yoshimoto

Miyamoto

Shimamura

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Histamine H3 receptors (H3Rs) are located on the presynaptic membranes and cell soma of histamine neurons, where they negatively regulate the synthesis and release of histamine. In addition, H3Rs are also located on nonhistaminergic neurons, acting as heteroreceptors to regulate the releases of other amines such as dopamine, serotonin, and norepinephrine. The present study investigated the effects of H3R ligands on appetite and body-weight regulation by using WT and H3R-deficient mice (H3RKO), because brain histamine plays a pivotal role in energy homeostasis. The results showed that thioperamide, an H3R inverse agonist, increases, whereas imetit, an H3R agonist, decreases appetite and body weight in diet-induced obese (DiO) WT mice. Moreover, in DiO WT mice, but not in DiO H3RKO mice, imetit reduced fat mass, plasma concentrations of leptin and insulin, and hepatic triglyceride content. The anorexigenic effects of imetit were associated with a reduction in histamine release, but a comparable reduction in histamine release with ␣-fluoromethylhistidine, an inhibitor of histamine synthesis, increased appetite. Moreover, the anorexigenic effects of imetit were independent of the melanocortin system, because imetit comparably reduced appetite in melanocortin 3 and 4 receptor-deficient mice. The results provide roles of H3Rs in energy homeostasis and suggest a therapeutic potential for H3R agonists in the treatment of obesity and diabetes mellitus.autoreceptor ͉ heteroreceptor ͉ appetite regulation O besity has recently become a matter of great concern, because it is considered one of the highest risk factors for diabetes mellitus, hyperlipidemia, and arteriosclerosis. To maintain body weight, caloric intake and energy expenditure must be balanced, and excessive caloric intake is a leading cause of obesity (1). There is growing evidence that the brain receives and integrates information related to energy status from peripheral tissues and that appetite is under the control of numerous neurotransmitters and hormones, such as neuropeptide Y, melanocortin, leptin, and ghrelin (2, 3)Histamine is a classical inflammatory mediator in peripheral tissues and also functions as a neurotransmitter in the brain. Histamine plays a pivotal role in various physiological functions, such as feeding behavior and energy homeostasis (4). Intracerebroventricular administration of histamine consistently decreases appetite in several species (4). Mice with genes disrupted for histamine H1 receptor or histidine decarboxylase (HDC), a ratelimiting enzyme for histamine synthesis, are prone to becoming obese on a high-fat diet or at advanced age (5-8). Furthermore, several antipsychotic drugs with high affinities for H1 receptors are known to cause weight gain in rodents and humans (9). These results suggest a significant role for histamine and H1 receptors in feeding behavior and body-weight regulation.Histamine H3 receptors (H3Rs) were pharmacologically identified more than a decade ago and recently cloned (10, 11). They are predominantly ex...

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Neuronal histamine in the hypothalamus suppresses food intake in rats

Cited by 117 publications

References 34 publications

Effect of histaminergic manipulation on weight in obese adults: a randomized placebo controlled trial

Effect of histaminergic manipulation on weight in obese adults: a randomized placebo controlled trial

Pleiotropic effect of histamine H4 receptor modulation in the central nervous system

Therapeutic potential of histamine H3 receptor agonist for the treatment of obesity and diabetes mellitus

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