Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracerebroventricular injections of 10-20-microg orexin-A induce food intake in rats for about 30 min, or enhance fasting-induced hyperphagia. In thermoregulatory studies, an amount of 2 microg of the peptide causes hypometabolism and hypothermia in the same period. The thermoregulatory reaction can be demonstrated at moderately cool environments, mainly after slight food deprivation. Both the ingestive and the thermoregulatory reactions are more pronounced in cold-adapted animals. Pretreatment with D-Tyr27,36,D-Thr32-NPY(27-36), a peptide-antagonist of NPY, prevents the hypothermia. It is concluded that, probably through NPY activation, orexin-A is involved primarily in the regulation of energy status of the body (as an anabolic agent), and not simply in the regulation of either food intake or body temperature. This anabolic response is followed by a late and more sustained catabolic phase characterized by absence of food intake, increased metabolism and dose-dependent hyperthermia, which hyperthermia cannot be suppressed by the NPY-antagonist. In contrast to orexin-A, neither hyperphagia nor suppression of refeeding hyperphagia, but dose-dependent hyperthermia follows injections of orexin-B, suggesting that this peptide has neither coordinated anabolic nor coordinated catabolic effects on energy balance.
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PMID:Effects of orexins on energy balance and thermoregulation. 1183 Feb 76

C75 is a potent inhibitor of fatty acid synthase that acts centrally to reduce food intake and body weight in mice; a single dose causes a rapid (>90%) decrease of food intake. These effects are associated with inhibition of fasting-induced up-regulation and down-regulation, respectively, of the expression of orexigenic (NPY and AgRP) and anorexigenic (POMC and CART) neuropeptide messages in the hypothalamus. Repeated administration of C75 at a submaximal level, however, differentially affected food intake of lean and obese mice. With lean mice, C75 suppressed food intake by approximately 50% and, with obese mice (ob/ob and dietary-induced obesity), by 85-95% during the first day of treatment. Lean mice, however, became tolerant/resistant to C75 over the next 2-5 days of treatment, with food intake returning to near normal and rebound hyperphagia occurring on cessation of treatment. In contrast, ob/ob obese mice responded to C75 with a >90% suppression of food intake throughout the same period with incipient tolerance becoming evident only after substantial weight loss had occurred. Dietary-induced obese mice exhibited intermediate behavior. In all cases, a substantial loss of body weight resulted. Pair-fed controls lost 24-50% less body weight than C75-treated mice, indicating that, in addition to suppressing food intake, C75 may increase energy expenditure. The decrease in body weight by ob/ob mice was due primarily to loss of body fat. In contrast to the short-term effects of C75 on "fasting-induced" changes of hypothalamic orexigenic and anorexigenic neuropeptide mRNAs, repeated administration of C75 either had the inverse or no effect as tolerance developed.
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PMID:Differential effects of a centrally acting fatty acid synthase inhibitor in lean and obese mice. 1185 92

Lactation is a physiological model for studying how the hypothalamus integrates peripheral signals, such as sensory signals (suckling stimulus) and those denoting energy balance (leptin), to alter hypothalamic function regulating food intake/energy balance and reproduction. The characteristics of food intake/energy balance during lactation are extreme hyperphagia, coupled with negative energy balance. The arcuate nucleus Neuropeptide Y (ARH-NPY) system is activated by: (1) brainstem projections specifically activated by the suckling stimulus, and (2) the decrease in leptin in response to the metabolic drain of milk production. NPY neurons from the ARH make direct contact with GnRH neurons and with CRH neurons in the PVH. NPY neurons also make contact with orexin and MCH neurons in the LHA, which, in turn, make contacts with GnRH neurons. Thus, the ARH-NPY system provides a neuroanatomical framework by which to integrate changes in food intake/energy with the regulation of cyclic reproductive function.
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PMID:Integration of the regulation of reproductive function and energy balance: lactation as a model. 1212 5

Neuronal responses to neuropeptide Y and dopamine were recorded in brain slices of hypothalamic paraventricular (PVH) and ventromedial (VMH) nuclei in normal and hyperphagic overweight rats reared in small litters of three pups. NPY significantly activated PVH neurons of normal rats, but inhibited neurons of overweight rats. In the VMH, a significantly higher coincidence of inhibition induced by NPY and dopamine was found in overweight rats. Similar neuronal responses were evoked by a NPY Y5 receptor agonist. Effects of NPY could be blocked by a Y1 receptor antagonist. The altered response of PVH neurons to the feeding-inducing NPY and the increased inhibition by NPY and dopamine in the VMH might contribute to the persisting hyperphagia and overweight of postnatally overnourished rats.
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PMID:Differential response to NPY of PVH and dopamine-responsive VMH neurons in overweight rats. 1221 98

The OLETF rat, lacking CCK-A receptors, provides an important model for identifying roles for CCK in the controls of food intake and body weight. OLETF rats are obese and diabetic and express deficits in the control of the size of individual meals. Meal size in OLETF rats is doubled and although meal number is decreased, the decrease is not sufficient to prevent hyperphagia. Analyses of patterns of hypothalamic gene expression in OLETF rats indicate the presence of a primary deficit in DMH NPY signaling. These data suggest an important role for CCK in controlling NPY expression in a population of non-leptin regulated hypothalamic neurons. In the absence of this control, NPY is overexpressed, contributing to hyperphagia and obesity. Thus, the obesity in the OLETF rats may be the outcome of two regulatory disruptions, one depending upon a peripheral within meal satiety pathway and the other depending upon a central pathway critical to overall energy balance.
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PMID:Actions of CCK in the controls of food intake and body weight: lessons from the CCK-A receptor deficient OLETF rat. 1235 7

Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, was originally purified from the rat stomach. We have previously reported that central administration of ghrelin increases food intake and body weight. To investigate the role of ghrelin in the hyperphagic response to uncontrolled diabetes, adult male rats were studied 14 days after administration of streptozotocin (STZ) or vehicle. STZ-treated diabetic rats were markedly hyperphagic. This hyperphagia was accompanied by hyperglycemia, hypoinsulinemia, and reduced plasma GH levels. Treatment of diabetic rats with insulin reversed these changes. Plasma ghrelin concentrations in untreated diabetic rats were significantly higher than in control rats and were normalized by insulin treatment. The ghrelin gene expression in the stomach was also higher in STZ diabetic rats than in control rats, but this difference was not significant. In contrast, plasma leptin was markedly reduced in STZ diabetic rats. This reduction in plasma leptin levels was reversed by insulin treatment. In addition, hypothalamic NPY mRNA levels were increased in STZ-treated diabetic rats and were reversed by insulin treatment. Furthermore, the hyperphagia was partially reversed by the administration of a ghrelin-receptor antagonist. Therefore, we conclude that the elevated plasma ghrelin levels, along with decreased plasma leptin levels, could contribute to the diabetic hyperphagia in part by increasing hypothalamic NPY. This is the first report to show the pathophysiological significance of ghrelin in diabetes.
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PMID:Role of ghrelin in streptozotocin-induced diabetic hyperphagia. 1244 21

Pregnancy is characterized by an increase in food intake that, in turn, produce a positive energy balance in order to face the considerable metabolic demands associated with the challenge of reproduction. Since hypothalamus is a key brain region involved in many peripheral signals and neuronal pathways that control energy homeostasis and food intake, we investigated if during pregnancy the increase in food intake is mediated by stimulating orexigenic and/or inhibiting anorexigenic neural pathways. We examined hypothalamic gene expressions of Ob-Rb, NPY, AgRP, POMC, MC4-R, and preproorexins in pregnant Wistar rats at day 19 of gestation. Food intake and body weight were increased progressively during the pregnancy. Visceral fat mass depots and serum leptin levels were also increased when compared with virgin animals. No differences were found in mRNA expression of Ob-Rb, POMC, MC4-R, NPY or preproorexin between virgin and pregnant animals. However, pregnancy produced a selective increase in AgRP mRNA levels. These results indicate that the positive energy balance that occurred during pregnancy can hardly be explained by changes in Ob-Rb despite hyperleptinemia associated with pregnancy. The enhanced expression of AgRP suggests the involvement of this neuropeptide in mediating pregnancy-associated hyperphagia.
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PMID:Pregnancy-induced hyperphagia is associated with increased gene expression of hypothalamic agouti-related peptide in rats. 1283 5

Pregnancy and lactation provide excellent models of physiological hyperphagia and hyperprolactinemia. To identify possible factors associated with the increased feeding in these situations, we measured hypothalamic mRNA levels of three orexigenic neuropeptides--NPY, MCH, and orexins--in nonpregnant, pregnant, and lactating rats by in situ hybridization. NPY mRNA content in the arcuate nucleus was significantly increased during pregnancy and lactation. However, MCH and prepro-orexin expression was decreased in both states. 48 or 72 h of fasting in pregnant and lactating rats further elevated NPY mRNA levels and increased the low MCH mRNA content. Surprisingly, no effect was observed in prepro-orexin mRNA levels. Finally, we investigated the possible effect of high PRL levels on these orexigenic signals using a model of hyperprolactinemia induced by pituitary graft. NPY mRNA content was unchanged, but MCH and prepro-orexin mRNA levels were significantly decreased. Our results suggest that the increased NPY expression might be partly responsible for the hyperphagia observed during pregnancy and lactation. MCH and prepro-orexin may be involved in the adaptation of other homeostatic mechanisms and their decreased levels in these physiological settings could be mediated by the elevated circulating PRL levels.
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PMID:Hypothalamic levels of NPY, MCH, and prepro-orexin mRNA during pregnancy and lactation in the rat: role of prolactin. 1289 Jun 92

Prader-Willi syndrome (PWS) is a genetic disorder characterized by mild mental retardation, short stature, abnormal body composition, muscular hypotonia and distinctive behavioural features. Excessive eating causes progressive obesity with increased cardiovascular morbidity and mortality. In the PWS genotype loss of one or more normally active paternal genes in region q11-13 on chromosome 15 is seen. It is supposed that the genetic alteration leads to dysfunction of several hypothalamic centres and growth hormone (GH) deficiency (GHD) is common. PWS is well described in children, in whom GH treatment improves body composition, linear growth, physical strength and agility. Few studies have focused on adults. We examined a cohort of 19 young adults with clinical PWS (13 with positive genotype) and mean BMI of 35 kg/m2. At baseline the activity of the GH-insulin-like growth factor-I (IGF-I) system was impaired with low GH values, low total IGF-I and in relation to the obesity low levels of free IGF-I and non-suppressed IGF-binding-protein-1 (IGFBP-1). 2/3 were hypogonadal. Bone mineral density (BMD) was low. Four patients had impaired glucose tolerance and nine patients high homeostasis model assessment (HOMA) index, indicating insulin resistance. Seven patients had a moderate dyslipidemia. The 13 patients with the PWS genotype were shorter and had significantly lower IGF-I. Seventeen (9 men and 8 women), subsequently completed a 12 months GH treatment trial, and GH had beneficial effects on body composition without significant adverse effects. The effects were more pronounced in the patients with the PWS genotype. Analysis of peptides involved in appetite regulation showed that leptin levels were high reflecting obesity and as a consequence NPY levels were low. In relation to the patients obesity circulating oxytocin levels were abnormally low and ghrelin levels abnormally high. Thus, oxytocin and ghrelin might be involved in the hyperphagia. NPY, leptin and ghrelin did not change during GH treatment. In conclusion this pilot study showed that adults with PWS have a partial GH deficiency, and GH treatment has beneficial effects on body composition in adult PWS without significant side-effects. Larger and longer term studies on the effect of GH replacement in adult PWS are encouraged.
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PMID:Endocrine and metabolic aspects of adult Prader-Willi syndrome with special emphasis on the effect of growth hormone treatment. 1470 May 52

In several hyperphagic models, including lactation, in which hypothalamic melanocortin signaling is reduced, a novel expression of NPY mRNA in the dorsomedial hypothalamus (DMH) has been observed, suggesting that melanocortin signaling and the induced NPY in the DMH may constitute unique neurocircuitry in mediating energy balance. Using lactating rats as a model, the present study first showed that in the DMH abundant alpha-MSH and agouti-related protein fibers are in close apposition to NPY-positive cells. However, no NPY and MC4R (a melanocortin receptor) double-labeled neurons were observed. These data suggested that melanocortin input may synapse on presynaptic terminals that then synapse on DMH NPY cells. To study the function of DMH MC4Rs in energy balance, an MC3/4R-selective agonist, melanotan II (MTII), was injected bilaterally into the DMH. MTII injection significantly suppressed feeding induced by 24 hr fasting or suckling-induced hyperphagia. Furthermore, MTII treatment greatly attenuated suckling-induced NPY expression in the DMH. MTII treatment also stimulated uncoupling protein 1 activity in the brown adipose tissue of suckling female rats, indicative of increased sympathetic outflow. In summary, the present study demonstrated that the melanocortin system in the DMH not only plays an important role in inducing NPY expression in the DMH of lactating rats but also in regulating energy homeostasis, at least in part, by modulating appetite and energy expenditure.
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PMID:Melanocortin 4 receptor-mediated hyperphagia and activation of neuropeptide Y expression in the dorsomedial hypothalamus during lactation. 1517 78


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