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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Food intake was restricted to 75% of ad libitum levels in 37 male Psammomys obesus (Israeli Sand Rats) from the ages of 4 (weaning) to 10 weeks. Energy restriction reduced the mean bodyweight at 10 weeks by 29% compared with 44 ad libitum fed controls. Hyperglycemia was prevented completely in the food-restricted group, and mean blood glucose concentrations were significantly reduced (3.8 +/- 0.2 vs. 5.5 +/- 0.4 mumol/L; p < 0.05) compared with control animals. Plasma insulin concentrations were also decreased significantly compared with ad libitum fed controls (105 +/- 13 vs. 241 +/- 29 mU/L; p < 0.05). Although energy restriction prevented hyperglycemia from developing in 10-week-old P. obesus, 19% of the food restricted animals still developed hyperinsulinemia. We concluded that hyperphagia between the ages of 4 to 10 weeks may be essential for the development of noninsulin-dependent diabetes mellitus in P. obesus, but that hyperinsulinemia may still occur in the absence of hyperphagia and hyperglycemia, suggesting a significant genetic influence on the development of hyperinsulinemia in this animal model.
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PMID:The effect of dietary energy restriction on body weight gain and the development of noninsulin-dependent diabetes mellitus (NIDDM) in Psammomys obesus. 919 93

In a series of studies on histaminergic functions in the hypothalamus, probes to manipulate activities of histaminergic neuron systems were applied to assess its physiologic and pathophysiologic implications using non-obese normal and Zucker obese rats, an animal model of genetic obesity. Food intake is suppressed by either activation of H1-receptor or inhibition of the H3-receptor in the ventromedial hypothalamus (VMH) or the paraventricular nucleus, each of which is involved in satiety regulation. Histamine neurons in the mesencephalic trigeminal sensory nucleus modulate masticatory functions, particularly eating speed through the mesencephalic trigeminal motor nucleus, and activation of the histamine neurons in the VMH suppress intake volume of feeding at meals. Energy deficiency in the brain, i.e., intraneuronal glucoprivation, activates neuronal histamine in the hypothalamus. Such low energy intake in turn accelerates glycogenolysis in the astrocytes to prevent the brain from energy deficit. Thus, both mastication and low energy intake act as afferent signals for activation of histaminergic nerve systems in the hypothalamus and result in enhancement of satiation. There is a rationale for efficacy of a very-low-calorie conventional Japanese diet as a therapeutic tool for weight reduction. Feeding circadian rhythm is modulated by manipulation of hypothalamic histamine neurons. Hypothalamic histamine neurons are activated by an increase in ambient temperature. Hypothalamic neuronal histamine controls adaptive behavior including a decrease in food intake and ambulation, and an increase in water intake to maintain body temperature to be normally constant. In addition, interleukin-1 beta, an endogenous pyrogen, enhanced turnover of neuronal histamine through prostaglandin E2 in the brain. Taken together, the histamine neuron system in the hypothalamus is essential for maintenance of thermoregulation through the direct and indirect control of adaptive behavior. Behavioral and metabolic abnormalities of obese Zucker rats including hyperphagia, disruption of feeding circadian rhythm, hyperlipidemia, hyperinsulinemia, and disturbance of thermoregulation are essentially derived from a defect in hypothalamic neuronal histamine. Abnormalities produced by depletion of neuronal histamine from the hypothalamus in normal rats mimic those of obese Zuckers. Grafting the lean Zucker fetal hypothalamus into the obese Zucker pups attenuates those abnormalities. These findings indicate that histamine nerve systems in the brain play a crucial role in maintaining homeostatic energy balance.
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PMID:Hypothalamic neuronal histamine: implications of its homeostatic control of energy metabolism. 922 31

The discovery of both neuropeptide Y and of leptin has led to a better understanding of the pathophysiology of obesity syndromes in animal models. It has strengthened the concept of the importance of the hypothalamus in the etiology of these syndromes. Due to alterations in the regulation of the hypothalamus, e.g. by insulin, by leptin or by decreases in the availability of glucose in specific brain areas, most animal models of obesity have higher than normal hypothalamic neuropeptide Y levels. As neuropeptide Y is a potent orexigenic agent, this hypothalamic defect explains why obese rodents are hyperphagic. Increased hypothalamic neuropeptide Y levels produce hyperinsulinemia and hypercorticism, two abnormalities previously reported in obesity, but whose origin is now known to be driven by neuropeptide Y. As hyperinsulinemia favors lipid accretion and muscle insulin resistance, and as hypercorticism favors the occurrence of both high circulating triglyceride levels and muscle insulin resistance, it may be appreciated that most disorders previously reported in obesity can now be explained by high hypothalamic neuropeptide Y levels. Leptin, produced and secreted by adipose tissue, is a potent anorectic agent whose main action is exerted within the hypothalamus in which it has been shown to decrease neuropeptide Y, therefore food intake. Leptin secretion is favored, in particular, by insulin as well as by glucocorticoids. When leptin is administered to obese mice of the ob/ob strain (which do not produce nor secrete leptin due to a gene mutation), their food intake, body weight and most metabolic abnormalities are normalized. However, in the majority of genetically obese rodents, as well as in obese humans, circulating levels of leptin are high. This is related to hyperinsulinemia- and hypercorticosteronemia-induced leptin oversecretion, as well as to central leptin receptor dysfunctions preventing normal leptin access to and action within specific brain areas. Under these conditions and to prevent the effects of elevated hypothalamic neuropeptide Y levels, neuropeptide Y antagonists or active leptin agonists must be found. Neuropeptide Y and leptin further underline the existence of functional relationship between the brain (hypothalamus) and the periphery (adipose tissue, muscle). Lack of leptin (mutated leptin gene) or inefficient leptin action (leptin receptor defect) results in increased hypothalamic neuropeptide Y levels. The latter favor hyperinsulinemia and hypercorticism both producing oversecretion of leptin which, when inefficient, cannot decrease neuropeptide Y: a vicious circle is created which maintains either a "thrifty phenotype" favoring fat depot or overt obesity, depending on the degree of hyperphagia.
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PMID:Central nervous system and body weight regulation. 923 33

New Zealand Obese (NZO) mice exhibit a polygenic syndrome of hyperphagia, obesity, hyperinsulinemia, and hyperglycemia similar to that observed in young diabetes mutant mice on the C57BLKS/J background (C57BLKS/J-Lepr(db)/Lepr(db)). Here we show that in NZO this syndrome is accompanied by a marked elevation of the leptin protein in adipose tissue and serum. The promoter region and the complementary DNA of the ob gene of NZO mice, including its 5'-untranslated region, are identical with the wild-type sequence (C57BL, BALB/c), except that the transcription start is located 5 bp upstream of the reported site. In contrast to C57BLKS/J+/+ and C57BL/6J-Lep(ob)/Lep(ob) mice, NZO mice failed to respond to recombinant leptin (7.2 microg/g) with a reduction of food intake. Leptin receptor messenger RNA as detected by PCR appears as abundant in hypothalamic tissue of NZO mice as in tissue from lean mice. Ten nucleotide polymorphisms are found in the complementary DNA of the leptin receptor, resulting in two conservative substitutions (V541I and V651I) in the extracellular part of the receptor and one nonconservative substitution (T1044I) in the intracellular domain between the presumed Jak and STAT binding boxes. However, these mutations are also present in the related lean New Zealand Black strain (body fat at 9 weeks: New Zealand Black, 6.2 +/- 1.3%; NZO, 17.0 +/- 1.7%). Thus, the polymorphic leptin receptor seems to play only a minor, if any, role in the obesity and hyperleptinemia of the NZO mouse. It is suggested that the main defect in NZO is located distal from the leptin receptor or at the level of leptin transport into the central nervous system.
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PMID:Hyperleptinemia, leptin resistance, and polymorphic leptin receptor in the New Zealand obese mouse. 932 35

The hypothalamic disorders of obesity include hyperphagia, a low central orthosympathetic tone (with reduced thermogenesis), vagal hyperinsulinism, low serotonin efficacy, a hyperactive hypothalamo-hypophyseal-adrenal axis, a hypoactive GHRH-GH-IGF axis and hypogonadism of central origin. Hyperlipogenesis, glucose intolerance and excessive gluconeogenesis are secondary features. Most frequently the hypothalamic ARC reacts poorly to the leptin hypersecreted by adipose tissue, so that the local synthesis of NPY is unchecked. Fortunately, two prostaglandins derived from dietary arachidonic acid bind fat cell PPAR gamma and hepatic PPAR alpha. Both nuclear proteins are phosphorylated through an insulin pathway, thereby inhibiting the expression of genes favoring obesity and stimulating that of genes accelerating fatty acid oxidation. The array of dietetic and pharmacologic tools considered today is analyzed.
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PMID:[Molecular endocrinology of hereditary obesity]. 949 39

1. Obesity is an undesirable side effect of neuroleptics which affects 50% approximately of patients under a program of chronic administration. 2. An animal model of neuroleptic-induced obesity and hyperphagia has been developed in female rats treated chronically with sulpiride (20 mg/Kg/ip. for 21 days). However, it is unknown whether or not the hyperphagia is essential for the development of this type of obesity. 3. Sulpiride or vehicle was administered in two experimental conditions: in the first one, food was available in an amount which was three times the previous individual daily food intake; in the second one, the daily food provision was maintained at the individual daily average before starting the treatments. This way hyperphagia was prevented in half of the groups. Besides the body weight gain measurement in all the groups, the serum levels of estradiol, prolactin, glucose and lipids were assessed in the groups with unrestricted food intake. 4. Food restriction prevented the sulpiride-induced weight gain, even though the rats displayed a permanent diestrus which suggests an hyperprolactinemia-induced impairment in the balance of the reproductive hormones that may promote weight gain. However, the basal levels of estradiol were not affected by sulpiride. 5. The high density cholesterol was significantly increased by sulpiride, and the serum glucose levels were significantly decreased, however these changes were only detected during the first week of treatment. 6. The decrease in the serum glucose levels may be an early consequence of hyperinsulinemia. 7. Neuroleptic-induced obesity in rats appears to mimic energy intake, endocrine status and carbohydrate metabolism in humans under chronic neuroleptic administration. However, these rodents did not display the typical changes in blood lipids observed in human obesity.
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PMID:Mechanism of the neuroleptic-induced obesity in female rats. 953 75

Some genes are expressed differently in earlier and later generations of most cell lines. Many diseases become clinically expressed only later in life, and show clustering of the age at onset in the affected siblings, which may be related to the changing expression with age of the genes involved. Because insulin and its receptor are extremely ancient and well preserved structures with almost universal mitogenic effects, insulin may serve a paradigm of this process. It is suggested that by stimulating cell proliferation, hyperinsulinemia speeds up the appearance of later generations of cells with different expression of the genes. Insulin resistance, accompanying any hyperinsulinemia and considered to be a pathogenetic factor of some common later-age diseases, involves only some biochemical, but not mitogenic effects of the hormone. In humans, high levels of insulin in blood are encountered both physiologically after meals and in many pathological conditions: insulin therapy inevitably causes peripheral hyperinsulinemia; in type 2 diabetes hyperinsulinemia precedes hyperglycemia by many years; hyperinsulinemia is an independent risk factor of atherosclerosis, of type 2 diabetes itself, of some forms of dementia and other diseases; obesity is an obligatory hyperinsulinemic condition. The opposite of hyperalimentation, i.e. calorie restriction (at least, in rodents) may exert its life-prolonging effects through decreasing insulinemia and therefore the rate of cell proliferation. Insulin is only one example, and different mitogens regulate proliferation of different cells. It is likely that growth factors in general accelerating the replication of cells, play a role in speeding up the appearance of later-age diseases involving these cells.
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PMID:Mitogenic factors accelerate later-age diseases: insulin as a paradigm. 966 95

Lesions of the most posterodorsal aspects of the amygdala in female rats result in hyperphagia and moderate obesity. In the present study, rats with amygdaloid lesions did not increase their daily food intake when their powdered diet was diluted with 25 or 50% nonnutritive bulk. Control animals adjusted their food intake appropriately. In a second study, rats with lesions ate less food (lab chow pellets) than controls when allowed to eat for only 1 h/day for 10 days. In experiment 3, rats were offered a three-choice macronutrient diet. Whereas four of six control animals preferred the high-fat diet, all eight of the rats with amygdaloid lesions displayed a distinct preference for the high-carbohydrate diet, including those that had preferred the high-fat diet before surgery. These results, along with the previous finding that identical lesions result in hyperinsulinemia, indicate that the amygdala is involved in both the homeostatic regulation of food (caloric) intake and the selection of macronutrients.
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PMID:Amygdaloid-lesion hyperphagia: impaired response to caloric challenges and altered macronutrient selection. 968 84

The cloning of mouse obesity genes and their human homologues provides unique opportunities to identify novel cellular targets for therapeutic intervention. The first of these to be cloned, agouti, antagonizes central nervous system melanocortin receptor (MCR) binding, resulting in hyperphagia and an obesity/hyperinsulinemia syndrome. There appears to be significant cross-talk between the agouti and leptin signaling systems. Agouti antagonism of central nervous system (CNS) MCR binding inhibits the anorexic effects of leptin, whereas agouti up-regulates adipocyte leptin expression, serving to limit the magnitude of agouti-induced obesity. The effects of agouti and leptin mutations on obesity, however, are independent and additive. Agouti also regulates adipocyte lipid metabolism, functioning both to increase the expression and activity of lipogenic genes and to inhibit lipolysis. Both of these actions occur via a Ca(2+)-dependent mechanism, suggesting that modulation of adipocyte Ca2+ transport may be a key target for further investigation.
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PMID:Agouti/melanocortin interactions with leptin pathways in obesity. 976 77

The mahogany (mg) locus originally was identified as a recessive suppressor of agouti, a locus encoding a skin peptide that modifies coat color by antagonizing the melanocyte-stimulating hormone receptor or MC1-R. Certain dominant alleles of agouti cause an obesity syndrome when ectopic expression of the peptide aberrantly antagonizes the MC4-R, a related melanocyte-stimulating hormone receptor expressed in hypothalamic circuitry and involved in the regulation of feeding behavior and metabolism. Recent work has demonstrated that mg, when homozygous, blocks not only the ability of agouti to induce a yellow coat color when expressed in the skin of the lethal yellow mouse (AY), but also the obesity resulting from ectopic expression of agouti in the brain. Detailed analysis of mg/mg AY/a animals, presented here, demonstrates that mg/mg blocks the obesity, hyperinsulinemia, and increased linear growth induced by ectopic expression of the agouti peptide. Remarkably, however, mg/mg did not reduce hyperphagia in the AY/a mouse. Furthermore, mg/mg induced hyperphagia and an increase in basal metabolic rate in the C57BL/6J mouse in the absence of AY. Consequently, although mahogany is broadly required for agouti peptide action, it also appears to be involved in the control of metabolic rate and feeding behavior independent of its suppression of agouti.
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PMID:Mahogany (mg) stimulates feeding and increases basal metabolic rate independent of its suppression of agouti. 977 May 50


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