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

We have previously produced human growth hormone (hGH) transgenic (TG) rats that show low circulating levels of both hGH and endogenous rat GH. Although body length of the TG rats is normal, they develop hyperphagia and severe obesity. The present study was undertaken to elucidate the causes of hyperphagia in the TG rats by focusing on temporal changes in plasma ghrelin levels and hypothalamic neuropeptide Y (NPY) contents. In both wild-type (WT) and TG rats, the highest value of plasma ghrelin levels was observed just before the dark phase, and thereafter plasma ghrelin levels were maintained higher in the TG than WT rats. Although NPY contents also showed the peak level just before the dark phase in both the arcuate (ARC) and paraventricular nuclei (PVN) of the hypothalamus, the values in the ARC, but not the PVN, of the TG rats was always lower than those of the WT rats, suggesting increased transport of NPY from the ARC to PVN in the TG rats. In addition, treatment with antagonists for Y1 and Y5 receptors for NPY reduced food intake much more effectively in the TG than WT rats. Intermittent treatment with recombinant hGH for a week significantly decreased food consumption, adipose tissue weight and plasma triglyceride concentrations in the TG rats. These results suggest that, in the TG rats, insufficiency in circulating GH stimulates the ghrelin-NPY system with a resultant increase in food intake.
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PMID:Involvement of neuropeptide Y in hyperphagia in human growth hormone transgenic rats. 1701 66

Centrally administered ghrelin, the endogenous agonist of the growth hormone secretegogue receptor, powerfully stimulates food intake. Although the orexigenic action of this peptide has been well established, it remains unclear whether ghrelin-induced hyperphagia is driven by energy needs or by reward. In our study ghrelin was injected into the lateral cerebral ventricle or the hypothalamic paraventricular nucleus of rats given a choice between a palatable yet calorie-dilute sucrose solution and a calorically dense chow. As a result of intraventricular and hypothalamic paraventricular ghrelin injections, animals increased intake of chow but not sucrose. When the sucrose solution was offered as the only source of calories, rats treated with ghrelin infused in the ventricle and site-specifically increased sucrose consumption. These results suggest that the primary effect of ghrelin is to stimulate food intake to satisfy energy needs.
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PMID:Central ghrelin induces feeding driven by energy needs not by reward. 1741 63

Binge eating and an increased role for palatability in determining food intake are abnormal adaptations in feeding behavior linked to eating disorders and body weight dysregulation. The present study tested the hypothesis that rats with limited access to highly preferred food would develop analogous opioid-dependent learned adaptations in feeding behavior, with associated changes in metabolism and anxiety-like behavior. For this purpose, adolescent female Wistar rats were daily food deprived (2 h) and then offered 10-min access to a feeder containing chow followed sequentially by 10-min access to a different feeder containing either chow (chow/chow; n=7) or a highly preferred, but macronutrient-comparable, sucrose-rich diet (chow/preferred; n=8). Chow/preferred-fed rats developed binge-like hyperphagia of preferred diet from the second feeder and anticipatory chow hypophagia from the first feeder with a time course suggesting associative learning. The feeding adaptations were dissociable in onset, across individuals, and in their dose-response to the opioid-receptor antagonist nalmefene, suggesting that they represent distinct palatability-motivated processes. Chow/preferred-fed rats showed increased anxiety-like behavior in relation to their propensity to binge as well as increased feed efficiency, body weight, and visceral adiposity. Chow/preferred-fed rats also had increased circulating leptin levels and decreased growth hormone and 'active' ghrelin levels. Thus, the short-term control of food intake in rats with restricted access to highly preferred foods comes to rely more on hedonic, rather than nutritional, properties of food, through associative learning mechanisms. Such rats show changes in ingestive, metabolic, endocrine, and anxiety-related measures, which resemble features of binge eating disorders or obesity.
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PMID:Opioid-dependent anticipatory negative contrast and binge-like eating in rats with limited access to highly preferred food. 1744 24

Prader-Willi syndrome is a rare genetic disorder, affecting 1 out of 25,000 births, in which a critical region of chromosome 15, the 15q11-q13 region, is affected. At birth, PWS infants exhibit severe hypotonia that partially improves, explaining in part suckling and swallowing troubles and the delay in psychomotor development. Characteristic facial features (dysmorphic syndrome) and very small hands and feet are frequently observed at this age. After this initial phase, the most striking signs appear: hyperphagia and absence of satiety often leading to severe obesity in affected children as young as two years. The situation may deteriorate quickly without adequate outside controls and explains in great part the morbidity and mortality of these patients. Other endocrine abnormalities in association with the hypothalamic-pituitary abnormalities contribute to the clinical picture of short stature due to a growth hormone deficiency and incomplete pubertal development. The degree of cognitive dysfunction varies widely from one child to another. It is associated with learning disabilities and impaired speech and language development worsened by psychological and behavioural troubles. The expert consensus is that diagnosis should be based on clinical criteria (Holm's criteria of 1993, revised in 2001) with confirmation by genetic study. Most cases are sporadic and familial cases are rare, those informations should be given as genetic counselling. It is necessary to set up a global and multidisciplinary management. Early diagnosis, early multidisciplinary care and growth hormone treatment have greatly improved the quality of life of these children. We have no long-term data on the effect of GH treatment in adults, on behavioural troubles and autonomy of the persons. In adults, complications particularly linked to obesity and problems of autonomy are still very important.
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PMID:[The Prader-Willi syndrome]. 1749 72

Ghrelin is produced primarily in the stomach in response to hunger, and circulates in the blood. Plasma ghrelin levels increase during fasting and decrease after ingesting glucose and lipid, but not protein. The efferent vagus nerve contributes to the fasting-induced increase in ghrelin secretion. Ghrelin secreted by the stomach stimulates the afferent vagus nerve and promotes food intake. Ghrelin also stimulates pituitary gland secretion of growth hormone (GH) via the afferent vagus nerve. GH inhibits stomach ghrelin secretion. These findings indicate that the vagal circuit between the central nervous system and stomach has a crucial role in regulating plasma ghrelin levels. Moreover, body mass index modulates plasma ghrelin levels. In a lean state and anorexia nervosa, plasma ghrelin levels are increased, whereas in obesity, except in Prader-Willi syndrome, plasma ghrelin levels are decreased and the feeding- and sleeping-induced decline in plasma ghrelin levels is disrupted. There are two forms of ghrelin: active n-octanoyl-modified ghrelin and des-acyl ghrelin. Fasting increases both ghrelin types compared with the fed state. Hyperphagia and obesity are likely to decrease plasma des-acyl ghrelin, but not n-octanoyl-modified ghrelin levels. Hypothalamic serum and glucocorticoid-inducible kinase-1 and serotonin 5-HT2C/1B receptor gene expression levels are likely to be proportional to plasma des-acyl ghrelin levels during fasting, whereas they are likely to be inversely proportional to plasma des-acyl ghrelin levels in an increased energy storage state such as obesity. Thus, a dysfunction of the ghrelin feedback systems might contribute to the pathophysiology of obesity and eating disorders.
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PMID:Ghrelin and feedback systems. 1798 56

A 16-year-old male adolescent diagnosed to have the Williams-Beuren syndrome was referred to our obesity outpatient clinic, due to his morbid obesity (body mass index 39.2 kilograms per square metre) and gluttony. After several unsuccessful dietary treatments, we started therapy with sibutramine. As growth hormone (GH) deficiency was diagnosed by an additional GH-stimulation test, we commenced with a GH-treatment. This well-tolerated combination therapy led to a remarkable weight loss of 10 kg and a growth-rate acceleration of 3.7 cm/year. Nine months after stopping the treatment with sibutramine, a partial weight gain was noticed. This case report justifies further research work on a combination therapy with sibutramine and GH for similar cases.
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PMID:Successful treatment of a morbidly obese and growth-retarded adolescent with Williams-Beuren Syndrome by combining the medication of growth hormone and sibutramine. 1820 53

Prader-Willi syndrome (PWS) is the leading genetic cause of obesity. After initial severe hypotonia, PWS children become hyperphagic and morbidly obese, if intake is not restricted. Short stature with abnormal growth hormone secretion, hypogonadism, cognitive impairment, anxiety and behavior problems are other features. PWS is caused by lack of expression of imprinted genes in a approximately 4 mb region of chromosome band 15q11.2. Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85) in PWS. To test this hypothesis, we created a approximately 150 kb deletion of the > 40 copies of Snord116 (Pwcr1/MBII-85) in C57BL/6 mice. Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation.
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PMID:SnoRNA Snord116 (Pwcr1/MBII-85) deletion causes growth deficiency and hyperphagia in mice. 1832 30

Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia, hyperphagia, childhood obesity at an early age, short stature, varying degrees of mental deficiency, and hypogonadism. In PWS, puberty is usually delayed and fails to complete, with most females never having regular menstrual cycles. We report a female patient with uniparental disomy, who experienced precocious puberty with menarche at age 8 years. The patient was treated with luteinizing hormone releasing hormone (LHRH) analog, which suppressed pubertal development. From our search of the literature this is the first application of LHRH analog to a female PWS patient for precocious puberty. Use of LHRH analog along with recombinant human growth hormone (rhGH) permitted stature closer to target height. The clinical course of this patient with PWS underscores the need for individualized treatment.
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PMID:Treatment of precocious puberty in a female with Prader-Willi syndrome. 1865 33

Prader-Willi syndrome (PWS) is a highly variable genetic disorder affecting multiple body systems whose most consistent major manifestations include hypotonia with poor suck and poor weight gain in infancy; mild mental retardation, hypogonadism, growth hormone insufficiency causing short stature for the family, early childhood-onset hyperphagia and obesity, characteristic appearance, and behavioral and sometimes psychiatric disturbance. Many more minor characteristics can be helpful in diagnosis and important in management. PWS is an example of a genetic condition involving genomic imprinting. It can occur by three main mechanisms, which lead to absence of expression of paternally inherited genes in the 15q11.2-q13 region: paternal microdeletion, maternal uniparental disomy, and imprinting defect.
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PMID:Prader-Willi syndrome. 1980 81

Growth hormone (GH) is an endocrine regulator of glucose and lipid metabolism as well as body growth. GH levels are decreased and a unique pulsatile secretory pattern becomes obvious after puberty particularly in males. Coincidentally with this, males tend to deposit body fat. Experimental and clinical evidence has accumulated that obesity is associated with a decrease in GH levels. A strain of transgenic rats has been generated with severe obesity but normal nose-to-tail length, which has low circulating GH levels without pulsatility (human growth hormone (hGH) transgenic rats). The present review mainly focuses on recent and current work analysing the relationship between the occurrence of obesity and low GH levels and/or the absence of GH pulsatility in this transgenic animal model. This model has elevated blood glucose, non-esterified fatty acid, insulin and leptin levels associated with hyperphagia, suggesting that these rats also carry insulin- and leptin-resistant characteristics. hGH transgenic rats were subjected to a pair-feeding treatment to normalize food intake and chronic GH replacement to normalize GH levels. While the pair-feeding for 8 weeks successfully suppressed body-weight gain, the fat pad : body weight ratio remained very similar to freely-eating control hGH transgenic rats, which indicates the hyperphagia is not the sole contributor to the excess fat accumulation in this model. However, continuous elevation of peripheral hGH levels (approximately 2-fold) for 8 weeks by means of a slow-release vehicle resulted in a significant decrease in the fat mass : body weight ratios by 30 %. This GH treatment altered neither food intake nor body-weight gain. Thus, two characteristic phenotypes observed in the hGH transgenic rats, hyperphagia and obesity, seem to be closely related to GH levels and GH secretory pattern. This relationship might be working in the regulation of changes in seasonal body composition in wild animals.
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PMID:Effects of pulsatile secretion of growth hormone (GH) on fat deposition in human GH transgenic rats. 1908 6


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