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

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

Ghrelin is a novel gastrointestinal peptide that stimulates growth hormone secretion, food intake, and body weight gain. Increased ghrelin secretion has been reported in such negative energy states as starvation and low body weight. We investigated the dynamics of ghrelin in rats with streptozotocin-induced diabetes, because they present reduced body weight and hyperphagia. The plasma ghrelin levels and gastric preproghrelin mRNA expression levels of the diabetic rats increased significantly and their gastric ghrelin levels decreased significantly. Negative energy balance may enhance preproghrelin mRNA expression and ghrelin secretion into the bloodstream.
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PMID:Enhanced plasma ghrelin levels in rats with streptozotocin-induced diabetes. 1270 20

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

The role of ghrelin in feeding control has been addressed from a largely hypothalamic perspective, with little attention directed at ingestive consequences of stimulation of the peptide's receptor, the growth hormone secretagogue receptor (GHS-R), in the caudal brainstem. Here, we demonstrate a hyperphagic response to stimulation of GHS-R in the caudal brainstem. Ghrelin (150 pmol) delivered to the third and fourth ventricles significantly and comparably increased cumulative food intake, with maximal response approximately 3 h after injection. The meal patterning effects underlying this hyperphagia were also similar for the two placements (i.e., significant reduction in the time between injection and first-meal onset, an increase in the number of meals taken shortly after the injection, and a trend toward an increase in the average size of the first meals that approached but did not achieve statistical significance). In a separate experiment, ghrelin microinjected unilaterally into the dorsal vagal complex (DVC) significantly increased food intake measured 1.5 and 3 h after treatment. The response was obtained with a 10-pmol dose, establishing the DVC as a site of action with at least comparable sensitivity to that reported for the arcuate nucleus. Taken together, the results affirm a caudal brainstem site of action and recommend further investigation into multisite interactions underlying the modulation of ingestive behavior by ghrelin.
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PMID:Hyperphagic effects of brainstem ghrelin administration. 1294 64

Ghrelin is a 28-amino acid peptide recently identified in the stomach as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a). Ghrelin is a potent stimulator of GH secretion. It was recently shown that circulating ghrelin levels in humans rise shortly before and fall shortly after every meal, and that ghrelin administration increases voluntary food intake. The hypothesis that ghrelin hypersecretion might contribute to genetic obesity has never been investigated. In this context, Prader-Willi syndrome is the most common form of human syndromic obesity. As ghrelin affects appetite as well as GH secretion and both are abnormal in PWS, it has been surmised that these alterations might be due to ghrelin dysregulation. The aim of the study was to investigate whether ghrelin is suppressed by the meals differently in PWS children than in PWS adults. Overnight circulating fasting ghrelin levels and ghrelin levels 120 min after breakfast were assayed in 7 PWS children (10.2 +/- 1.7 yr), 7 subjects with morbid obesity (10.3 +/- 1.3 yr), and 5 normal controls (8.4 +/- 1.4 yr). Because of the data spread, no statistical difference was observed in fasting ghrelin levels between PWS and control children (p = NS); anyway, fasting ghrelin levels were significantly lower in obese children than in the other groups (p < 0.05 vs. control and PWS children). Ghrelin levels were slightly suppressed by the meal in control subjects (mean fasting ghrelin: 160.2 +/- 82 pg/ml; after the meal, 141.2 +/- 57 pg/ml, p = NS); the meal failed to suppress ghrelin levels in obese children (mean fasting ghrelin: 126.4 +/- 8.5 pg/ml; after the meal, 119.1 +/- 8.3 pg/ml, p = NS). Interestingly, the meal markedly suppressed ghrelin levels in PWS children (mean fasting ghrelin: 229.5 +/- 70.4 pg/ml; after the meal, 155.8 +/- 34.2 pg/ml, p < 0.01). In conclusion, since a lack of decrease in circulating ghrelin induced by the meal was previously reported in PWS adults, the finding of a meal-induced decrease in ghrelin levels in our population of young PWS would imply that the regulation of the ghrelin system involved in the orexigenic effects of the peptide is operative during childhood, although it progressively deteriorates and is absent in adulthood when hyperphagia and obesity progressively worsen.
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PMID:Maintenance of a normal meal-induced decrease in plasma ghrelin levels in children with Prader-Willi syndrome. 1505 69

Ghrelin is a recently identified growth hormone (GH) secretogogue whose administration not only induces GH release but also stimulates food intake, increases adiposity, and reduces fat utilization in mice. The effect on food intake appears to be independent of GH release and instead due to direct activation of orexigenic neurons in the arcuate nucleus of the hypothalamus. The effects of ghrelin administration on food intake have led to the suggestion that inhibitors of endogenous ghrelin could be useful in curbing appetite and combating obesity. To further study the role of endogenous ghrelin in appetite and body weight regulation, we generated ghrelin-deficient (ghrl(-/-)) mice, in which the ghrelin gene was precisely replaced with a lacZ reporter gene. ghrl(-/-) mice were viable and exhibited normal growth rates as well as normal spontaneous food intake patterns, normal basal levels of hypothalamic orexigenic and anorexigenic neuropeptides, and no impairment of reflexive hyperphagia after fasting. These results indicate that endogenous ghrelin is not an essential regulator of food intake and has, at most, a redundant role in the regulation of appetite. However, analyses of ghrl(-/-) mice demonstrate that endogenous ghrelin plays a prominent role in determining the type of metabolic substrate (i.e., fat vs. carbohydrate) that is used for maintenance of energy balance, particularly under conditions of high fat intake.
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PMID:Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. 1514 84

Ghrelin and peptide YY (PYY) are peptides generally produced by the gastrointestinal organs which are involved in appetite regulation via highly specialized centers in the brain. Abnormal plasma ghrelin and PYY levels compared with controls have been reported for subjects with Prader-Willi syndrome (PWS) which is characterized by infantile hypotonia, poor suck reflex and failure to thrive followed by hyperphagia and marked obesity in early childhood. We studied gene expression of ghrelin, peptide YY, and their receptors (i.e., GHS-R1a, GHS-R1b, and NPY2R) in six different brain regions (frontal cortex, temporal cortex, visual cortex, pons, medulla, and hypothalamus) obtained from three subjects with PWS, two individuals with Angelman syndrome, and six controls to determine if expression of these genes is detectable in different regions of the brain in subjects with and without PWS. In general, expression of these genes using RT-PCR was detected in all subjects and no obvious differences were seen in their pattern of expression between subjects with or without PWS. Additional studies including quantitative gene expression measurements will be required to further evaluate the role of these genes in the eating disorder seen in PWS.
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PMID:Ghrelin, peptide YY and their receptors: gene expression in brain from subjects with and without Prader-Willi syndrome. 1575 36

Prader-Willi syndrome (PWS) has a biphasic clinical phenotype with failure to thrive in the neonatal period followed by hyperphagia and severe obesity commencing in childhood among other endocrinological and neurobehavioral abnormalities. The syndrome results from loss of function of several clustered, paternally expressed genes in chromosome 15q11-q13. PWS is assumed to result from a hypothalamic defect, but the pathophysiological basis of the disorder is unknown. We hypothesize that a fetal developmental abnormality in PWS leads to the neonatal phenotype, whereas the adult phenotype results from a failure in compensatory mechanisms. To address this hypothesis and better characterize the neonatal failure to thrive phenotype during postnatal life, we studied a transgenic deletion PWS (TgPWS) mouse model that shares similarities with the first stage of the human syndrome. TgPWS mice have fetal and neonatal growth retardation associated with profoundly reduced insulin and glucagon levels. Consistent with growth retardation, TgPWS mice have deregulated liver expression of IGF system components, as revealed by quantitative gene expression studies. Lethality in TgPWS mice appears to result from severe hypoglycemia after postnatal d 2 after depletion of liver glycogen stores. Consistent with hypoglycemia, TgPWS mice appear to have increased fat oxidation. Ghrelin levels increase in TgPWS reciprocally with the falling glucose levels, suggesting that the rise in ghrelin reported in PWS patients may be secondary to a perceived energy deficiency. Together, the data reveal defects in endocrine pancreatic function as well as glucose and hepatic energy metabolism that may underlie the neonatal phenotype of PWS.
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PMID:Hormonal and metabolic defects in a prader-willi syndrome mouse model with neonatal failure to thrive. 1600 20

Ghrelin, an orexigenic peptide produced in the stomach, is increased in streptozotocin (STZ)-induced diabetic (DM) mice. This study clarifies the regulation of ghrelin levels by leptin in STZ-DM mice. STZ-DM mice had higher plasma ghrelin concentrations and greater ghrelin mRNA expression than control mice. Changes in ghrelin levels were dose dependently attenuated by the subcutaneous injection of leptin (0-27 nmol x kg(-1) x day(-1) over 7 days). Leptin treatment also partially reversed the hyperphagia and hyperglycemia observed in STZ-DM mice, but not the hypoinsulinemia, and there was a decrease in plasma ghrelin concentrations and ghrelin mRNA levels compared with STZ-LEP pair-fed mice. These results indicate that leptin treatment partially reverses elevated plasma ghrelin levels in STZ-DM mice independent of food intake and insulin, and suggest that hypoleptinemia in STZ-DM mice upregulates ghrelin.
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PMID:Leptin downregulates ghrelin levels in streptozotocin-induced diabetic mice. 1610 2

The gut peptide ghrelin has been shown to stimulate food intake after both peripheral and central administration, and the hypothalamic arcuate nucleus has been proposed to be the major site for mediating this feeding stimulatory action. Ghrelin receptors are widely distributed in the brain, and hindbrain ghrelin administration has been shown to potently stimulate feeding, suggesting that there may be other sites for ghrelin action. In the present study, we have further assessed potential sites for ghrelin action by comparing the ability of lateral and fourth ventricular ghrelin administration to stimulate food intake and alter patterns of hypothalamic gene expression. Ghrelin (0.32, 1, or 3.2 nmol) in the lateral or fourth ventricle significantly increased food intake in the first 4 h after injection, with no ventricle-dependent differences in degree or time course of hyperphagia. One nanomole of ghrelin into either the lateral or fourth ventricle resulted in similar increases in arcuate nucleus neuropeptide Y mRNA expression. Expression levels of agouti-related peptide or proopiomelanocortin mRNA were not affected by ghrelin administration. These data demonstrate that ghrelin can affect food intake and hypothalamic gene expression through interactions at multiple brain sites.
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PMID:Lateral ventricular ghrelin and fourth ventricular ghrelin induce similar increases in food intake and patterns of hypothalamic gene expression. 1642 82


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