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)

Melanin-concentrating hormone (MCH) and orexin-A are orexigenic peptidergic neurotransmitters produced primarily in the lateral hypothalamus. Because two other hypothalamic peptides, neuropeptide Y and agouti-related peptide, increase food intake by a mechanism that depends on activation of opioid receptors, we assessed whether MCH or orexin-A also elicits food intake via opioid receptor activation. A dose of naloxone (0.3 mg/kg, ip) that had no effect on its own reduced the acute orexigenic effect of third ventricular (i3vt) orexin-A (3 ng/rat). However, this same dose of naloxone had no effect on i3vt MCH (5 microg/rat)-induced hyperphagia. Because the opioid system has also been linked to food selection, we investigated whether MCH or orexin-A alters food choice when rats have simultaneous access to two diets differing in the relative amounts of fat and carbohydrate. Whereas i3vt MCH stimulated intake of both diets and did not alter food choice, i3vt orexin-A stimulated intake of only the high fat diet. These data indicate that despite several similarities between MCH and orexin-A, these two lateral hypothalamic area peptides stimulate food intake by recruiting different neural circuits and exert different effects on food choice.
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PMID:Eating elicited by orexin-a, but not melanin-concentrating hormone, is opioid mediated. 1213 May 65

Orexins are endogenous neuropeptides that potently facilitate appetite and food consumption. In the present study, we examined orexin immunoreactivity and prepro-orexin mRNA expression in the lateral hypothalamus by immunohistochemistry and competitive reverse transcription-polymerase chain reaction (RT-PCR) methods in different models of hyperphagia in rats. Hyperphagia was induced by lesions of either the ventromedial hypothalamus (VMHL) or the paraventricular nucleus (PVNL), and we also compared lactating rats to nonlactating controls. Both VMHL and PVNL increased food intake and body weight compared to shams. On day 7 post lesion, serum leptin and insulin concentrations exhibited 3.2- and 2.8-fold increases in VMHL rats, and nonsignificant 1.8- and 1.8-fold increases in PVNL rats; there were significant decreases (48% and 33%) in lactating rats on day 12 postpartum compared to controls, respectively. Serum glucose concentrations were not significantly changed compared to controls in these rats. Quantification by image analysis suggests that VMHL significantly decreased the number and mean staining intensity of orexin-A immunoreactive neurones compared to those in the sham-lesioned group; while PVNL did not change orexin-A immunoreactivity. Competitive RT-PCR analysis showed that VMHL significantly decreased the prepro-orexin mRNA expression compared to those in the sham-lesioned group, and PVNL did not change it. Lactating rats on days 11-12 of lactation had significantly greater number and mean staining intensity of orexin-A immunoreactive neurones, prepro-orexin mRNA expression food intake and body weight than nonlactating postpartum rats. Thus, changes in orexin-A immunoreactivity and prepro-orexin mRNA expression were not consistent between the hyperphagia models. These results suggest that the hyperphagia from VMHL or PVNL and lactating rats differ in their involvement of orexin-A, and the change in circulating leptin and insulin concentrations may be involved in the change of orexin-A immunoreactivity in these rats.
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PMID:Orexin-A immunoreactivity and prepro-orexin mRNA expression in hyperphagic rats induced by hypothalamic lesions and lactation. 1253 69

Ghrelin stimulates feeding when administered centrally and peripherally. The lateral hypothalamus (LH) is thought to mediate ghrelin-induced hyperphagia. Thus, we examined central mechanisms underlying feeding generated by LH ghrelin. We determined that 0.3nmol of LH-injected ghrelin was the lowest dose increasing food consumption and it induced Fos immunoreactivity (IR; a marker of neuronal activation) in feeding-related brain areas, including the hypothalamic paraventricular, arcuate, and dorsomedial nuclei, amygdala, and nucleus of the solitary tract. Also, LH ghrelin induced Fos IR in LH orexin neurons. We conclude that the LH, as part of larger central circuitry, integrates orexigenic properties of ghrelin.
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PMID:Neural basis of orexigenic effects of ghrelin acting within lateral hypothalamus. 1286 Feb 4

Rat cisternal (CSF) hypocretin-1 in cerebrospinal fluid was measured after 6 or 96 h of REM sleep deprivation and following 24 h of REM sleep rebound. REM deprivation was found to increase CSF hypocretin-1 collected at zeitgeber time (ZT) 8 but not ZT0. Decreased CSF hypocretin levels were also observed at ZT8 after 24 h of REM sleep rebound. These results suggest that REM sleep deprivation activates and REM sleep rebound inhibits the hypocretin system. Increased hypocretin tone during REM deprivation may be important in mediating some of the effects of REM sleep deprivation such as antidepressant effects, hyperphagia and increased sympathetic activity.
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PMID:Increased hypocretin-1 levels in cerebrospinal fluid after REM sleep deprivation. 1464 64

Food intake is regulated by hypothalamic neuropeptides which respond to peripheral signals. Plasma ghrelin and leptin levels reflect peripheral energy balance and regulate hypothalamic neuropeptides such as neuropeptide Y (NPY), pro-opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), melanin-concentrating hormone (MCH), and orexins. Thyroid hormone stimulates food intake in humans and rodents. However, the mechanisms responsible for this stimulation have not been fully elucidated. To investigate the hyperphagic response to triiodothyronine (T(3))-induced thyrotoxicosis, adult male rats were studied 7 days after daily intraperitoneal injections of T(3) or vehicle. T(3)-treated rats were markedly hyperphagic. During this hyperphagia, plasma leptin levels were markedly decreased. However, the expression of the ghrelin gene in the stomach and the plasma ghrelin concentrations did not differ between the 2 groups. Hypothalamic NPY mRNA levels were significantly increased and associated with a marked decreased in both hypothalamic POMC and CART mRNA levels in the T(3)-treated rats. Hypothalamic MCH and orexin mRNA levels did not differ between the 2 groups. In addition, hyperphagia was partially reversed by intracerebroventricular administration of the NPY Y1 receptor antagonist BIBO3304. Therefore, the decreased plasma leptin levels could contribute to hyperphagia in T(3)-induced thyrotoxicosis. However, plasma ghrelin levels did not contribute to this hyperphagia.
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PMID:Hypothalamic neuropeptide Y/Y1 receptor pathway activated by a reduction in circulating leptin, but not by an increase in circulating ghrelin, contributes to hyperphagia associated with triiodothyronine-induced thyrotoxicosis. 1468 45

Gamma-amino butyric acid (GABA)A receptor stimulation in the nucleus accumbens shell produces intense hyperphagia in rats and increases Fos expression in the lateral hypothalamus. To explore the involvement of hypothalamic orexin/hypocretin- or melanin concentrating hormone-immunoreactive neurons in this effect, the GABAA agonist, muscimol (0, 50 ng), was infused directly into the nucleus accumbens shell of rats; 90 min later, their brains were collected and subsequently processed for immunohistochemistry. A group exposed to a novel environment was included to evaluate the specificity of Fos expression changes with regard to general arousal. Alternating sections through the hypothalamus were double-stained for orexin/hypocretin-Fos or melanin concentrating hormone-Fos combinations. Intra-accumbens shell muscimol treatment significantly increased the percentage of orexin/hypocretin-containing neurons expressing Fos in the lateral, but not medial, portion of the perifornical/lateral hypothalamic area. Regardless of treatment condition, greater percentages of orexin/hypocretin-containing neurons in the medial portion of the hypothalamus expressed Fos relative to cells located more laterally. None of the manipulations increased Fos expression in melanin concentrating hormone-immunoreactive neurons. Muscimol treatment also markedly increased Fos expression in the arcuate nucleus, which connects reciprocally to the lateral/perifornical hypothalamic area. Thus, orexin/hypocretin-containing neurons in lateral sectors of the hypothalamus, along with cells in the arcuate nucleus, display phasic increases in Fos expression after an orexigenic pharmacological manipulation of the nucleus accumbens shell, but to a lesser degree after the heightened arousal associated with exposure to a novel environment.
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PMID:Activation of a subpopulation of orexin/hypocretin-containing hypothalamic neurons by GABAA receptor-mediated inhibition of the nucleus accumbens shell, but not by exposure to a novel environment. 1472 32

Removal of glucocorticoids by adrenalectomy (ADX) reduces food intake and body weight in rodents and prevents excessive weight gain in many genetic and dietary models of obesity. Glucocorticoids play a key role to promote positive energy balance in normal and pathological conditions, at least in part, by altering the sensitivity to hypothalamic peptides. The hyperphagia after central neuropeptide Y administration, for example, is attenuated by ADX, and there is evidence that glucocorticoids influence both MCH and orexin A activity. In the present study, feeding responses to third ventricular MCH and orexin A were measured in rats after bilateral ADX or sham surgery. ADX rats were significantly less sensitive to the orexigenic action of third ventricular MCH, whereas orexin A-induced hyperphagia was unaffected. Replacement of corticosterone in the drinking water of ADX rats reversed the effects of ADX on MCH sensitivity. Although we found significant populations of glucocorticoid receptors in the lateral hypothalamus, none were colocalized with either MCH or orexin A-containing cell bodies. Furthermore, whereas ADX significantly reduced hypothalamic MCH and orexin gene expression, this could not be restored by glucocorticoids in the drinking water. Collectively, the present data suggest that glucocorticoids may promote food intake in part by potentiating the orexigenic actions of MCH without affecting the actions of orexin A and that glucocorticoids act indirectly to influence the effects of MCH on food intake.
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PMID:Differential effects of adrenalectomy on melanin-concentrating hormone and orexin A. 1504 62

Little is known about the impact of circulating lipids on brain processes. Building on evidence that chronic fat consumption stimulates hypothalamic peptides in close association with elevated triglycerides (TG), this study examined whether an acute rise in TG levels induced by fat emulsion can affect these hypothalamic systems. In normal weight rats, ip injection of Intralipid (20%, 5 ml) during the first 4 h after injection produced a robust increase in TG levels and nonesterified fatty acids, but had no impact on glucose, insulin, or leptin levels. This was accompanied by a marked increase in the expression of particular orexigenic peptides, galanin, orexins, and the opioid, enkephalin, which are known to be positively related to fat ingestion. This effect, similarly induced by 4 h of high fat diet consumption, was detected in the paraventricular nucleus (PVN) for galanin, in the perifornical hypothalamus (PFH) for orexins, and in the PVN, PFH, as well as the arcuate nucleus (ARC) for enkephalin. It was not seen, however, for neuropeptide Y and agouti-related protein localized in the ARC, which are unaffected or reduced by dietary fat. This site specificity was confirmed by c-Fos immunostaining, a marker of neuronal activity, which was increased by Intralipid in the PVN and PFH, but not in the ARC, and was detected in 20% of orexin-expressing neurons in the PFH. These findings suggest that circulating lipids, through different mechanisms, may stimulate hypothalamic neurons, which synthesize specific feeding stimulatory peptides that possibly contribute to hyperphagia during consumption of a fat-rich diet.
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PMID:Circulating triglycerides impact on orexigenic peptides and neuronal activity in hypothalamus. 1511 77

Orexin-A is a novel neuropeptide produced by neurons mainly located in lateral hypothalamic area that potently facilitates appetite and food intake. The purpose of this study was to investigate the possible change in orexin-A immunoreactivity in suckling-induced hyperphagia. By using immunohistochemistry and image analysis techniques we examined orexin-A-like immunoreactivity in a series of rat brain sections corresponding to the hypothalamus in groups of non-lactating, lactating, lactating with overnight cessation of suckling, lactating and cessation followed by resumed short-term sucklings. Long-term lactation significantly increased daily food intake on day 3 (81%) and day 11 (180%) postpartum compared to that in non-lactating postpartum rats, whereas daily food intake was significantly decreased by overnight cessation of suckling on day 11 postpartum in long-term lactating rats (45%). Moreover, long-term lactating rats on day 12 postpartum exhibited significantly greater number and higher mean staining intensity of orexin-A immunoreactive neurons than those of non-suckling postpartum rats (P<0.001 and P<0.05, respectively). Overnight cessation of lactation in rats on day 12 postpartum significantly decreased both the number and mean staining intensity of orexin-A immunoreactive neurons compared to those in long-term lactating group of rats (P<0.001 and P<0.05, respectively), similar to the levels in the non-lactating postpartum rats. Resumed lactation for 2 and 5 h after overnight cessation of lactation significantly increased the number (P<0.001 and P<0.05, respectively) and mean staining intensity (P<0.05) of orexin-A immunoreactive neurons compared to those in the rats without resumed lactation. Both long-term lactation and short-term resumed suckling enhanced orexin-A immunoreactivity in the hypothalamus in rats, and overnight cessation of lactation down-regulated the increased orexin-A immunoreactivity induced by long-term lactation. Suckling may regulate orexin-A expression in the hypothalamus and the increased orexin-A may be involved in hyperphagia in lactating rats, suggesting the possibility of the existence of some neural-humoral links between suckling and hypothalamic orexin-A-immunoreactive neurons.
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PMID:[Effects of lactation, lactation-cessation and lactation-cessation-lactation paradigms on hypothalamic orexin-A immunoreactive neurons in rats]. 1561 15

The influence of cholecystokinin octapeptide (CCK-8) on normal and insulin-induced feeding and expression of orexigenic hypothalamic neuropeptides was investigated in male rats. CCK-8, administered during meals (4 microg/kg) or continuously (32 microg/kg over 60 min), blunted the stimulating effect of insulin (50 IU/kg) on feeding by reducing meal size (-60%; P<0.05 or -86%; P<0.0001, respectively). Rats without access to food and injected with IP insulin (50 IU/kg) showed increased hypothalamic mRNA levels of orexin (+30%; P<0.05) and melanin-concentrating hormone (+52%; P<0.05), as compared with ad libitum-fed and saline-injected control rats. Continuous IP infusion of CCK-8 (32 microg/kg) blunted these increases. Our results suggest that both orexin and melanin-concentrating hormone participate in the response to insulin hypoglycemia without food being present; these neurons may be involved in mechanisms related to insulin-induced hyperphagia. Signals triggered by peripheral CCK-8 act to decrease the expression of orexin and melanin-concentrating hormone. This may be associated with a reduction in hyperphagia.
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PMID:Effect of CCK-8 on insulin-induced hyperphagia and hypothalamic orexigenic neuropeptide expression in the rat. 1565 51


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