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      Histamine and the Regulation of Body Weight

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          Energy intake and expenditure is regulated by a complex interplay between peripheral and central factors. An exhaustive list of peptides and neurotransmitters taking part in this complex regulation of body weight exists. Among these is histamine, which acts as a central neurotransmitter. In the present article we review current evidence pointing at an important role of histamine in the regulation of appetite and metabolism. Studies using both knockout mouse models as well as pharmacological studies have revealed that histamine acts as an anorexigenic agent via stimulation of histamine H<sub>1</sub> receptors. One effect of histamine in the regulation of appetite is to act as a mediator of the inhibitory effect of leptin on appetite. It seems that histamine may attenuate and delay the development of leptin resistance in high-fat-diet-induced obesity. Furthermore, histamine may also act to accelerate lipolysis. Based on the current evidence of the involvement of histamine in the regulation of body weight, the histaminergic system is an obvious target for the development of pharmacological agents to control obesity. At present, H<sub>3</sub> receptor antagonists that stimulate the histaminergic system may be the most promising histaminergic drugs for antiobesity therapy.

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          Most cited references 30

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          Epidemiologic aspects of overweight and obesity in the United States.

          National survey data from the U.S. show that the prevalence of overweight and obesity among adults remained relatively constant over the 20-year period from 1960 to 1980, began to increase around the mid-1980s and has continued to increase. Data for children and adolescents, based on different definitions, show the same pattern. It can sometimes be more useful to look at the whole distribution of body mass index, rather than on prevalence estimates based on pre-defined cutoffs. Data from several countries suggest that for both adults and children, the distribution of BMI has become more skewed over time. Although many hypotheses have been put forward about the causes of the increases, data to address these issues are sparse. Obesity is a well-known risk factor for numerous health conditions. Nonetheless, the health consequences of the increases in obesity have not been fully delineated. Increases in diabetes have been noted in conjunction with the rise in obesity. On the other hand, declines in some other cardiovascular risk factors have been seen at all BMI levels. Rising life expectancy and decreasing heart disease mortality rates seem to confound some of the expectations about the effects of increasing obesity on mortality. The effects of obesity on morbidity may be greater than its effects on mortality. The increasing prevalence of obesity poses challenges for researchers and for policy makers.
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            Highly potent and selective ligands for histamine H3-receptors.

            New drugs selective for histamine H3-receptors can be used to establish that these receptors are involved in the feedback control of histamine synthesis and release, and to demonstrate their distribution in the brain and peripheral tissues. These drugs provide new tools for affecting physiological and possibly pathological conditions in which histamine is involved.
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              Involvement of hypothalamic histamine H1 receptor in the regulation of feeding rhythm and obesity.

              Histamine H(1) receptors (H(1)-Rs) are found in peripheral tissues and in regions of the hypothalamus that are concerned with regulating body composition. In the present study, we investigated the detailed mechanisms of histamine H(1)-Rs in the development of obesity. Histamine H(1)-R knockout (H1KO) mice gradually developed mature-onset obesity, which was accompanied by hyperphagia and decreased expression of uncoupling protein-1 (UCP-1) mRNA. Both younger nonobese (12-week-old) and older obese (48-week-old) H1KO mice exhibited impairment of the responsiveness to the leptin. In addition, disruption of the diurnal rhythm of feeding occurred before the onset of obesity in H1KO mice. Correction of these abnormal feeding rhythms by means of scheduled feeding caused a reduction in obesity and associated metabolic disorders in H1KO mice. Furthermore, central administration of a histamine H(1)-R agonist affected feeding behavior, body weight, and c-fos-like immunoreactivity in the hypothalamus. Taken together, these findings suggest that histamine H(1)-Rs are crucial for the regulation of feeding rhythm and in mediating the effects of leptin. Early disruption of H(1)-R-mediated functions in H1KO mice may lead to hyperphagia and decreased expression of UCP-1 mRNA, which may contribute to the development of obesity in these animals. In addition, centrally acting histamine H(1)-R may be a novel therapeutic target for the treatment of obesity and related metabolic disorders.

                Author and article information

                S. Karger AG
                November 2007
                11 September 2007
                : 86
                : 3
                : 210-214
                aCluster for Molecular Imaging, University of Copenhagen, bDepartment of Clinical Physiology, Nuclear Medicine and PET, and cDepartment of Surgery C, Rigshospitalet, Copenhagen, Denmark
                108341 Neuroendocrinology 2007;86:210–214
                © 2007 S. Karger AG, Basel

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                Page count
                References: 47, Pages: 5


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