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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ghrelin induces obesity via central and peripheral mechanisms. Administration of ghrelin leads to increased food intake and decreased fat utilisation in rodents. Ghrelin levels are decreased in obese individuals. Recently, a polymorphism (Arg-51-Gln) within the ghrelin gene (GHRL) was described to be associated with obesity. We screened the GHRL coding region in 215 extremely obese German Children and adolescents (study group 1) and 93 normal weight students (study group 2) by single strand conformation polymorphism analysis (SSCP). We found the two previously described single nucleotide polymorphisms (SNP: Arg-51-Gln and Leu-72-Met) in similar frequencies in study groups 1 and 2 (allele frequencies were: 0.019 and 0.016 for the 51-Gln allele and 0.091 and 0.086 for the 72-Met allele, respectively). Hence, we could not confirm the previous finding. Additionally, two novel variants were identified within the coding region: (1) We detected one healthy normal weight individual with a frameshift mutation (2bp deletion at codon 34). This frameshift mutation affects the coding region of the mature ghrelin. Hence, it is highly likely that the normal weight student is haplo-insufficient for ghrelin. (2) An A to T transversion leads to an amino acid exchange from Gln to Leu at amino acid position 90. The frequency of the 90-Leu allele was significantly higher in the extremely obese children and adolescents (0.063) than in the normal weight students (0.016; nominal p = 0.011). Additionally, we genotyped 134 underweight students and 44 normal weight adults for this SNP. Genotype frequencies were similar in extremely obese children and adolescents, underweight students and normal weight adults (p > 0.8). In conclusion, we identified four sequence variants in the coding region of the ghrelin gene in individuals belonging to different weight extremes. A frameshift mutation was detected in a normal weight individual. None of the variants seem to influence weight regulation.
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PMID:Ghrelin gene: identification of missense variants and a frameshift mutation in extremely obese children and adolescents and healthy normal weight students. 1205 Feb 39

Obesity is important in the aetiology of type 2 diabetes, and presents a major barrier to its successful prevention and management. Obesity develops when energy intake exceeds energy expenditure over time. A complex system has evolved to maintain energy homeostasis, but this is biased towards weight gain. Meal size is controlled by a series of short-term hormonal and neural signals that derive from the gastrointestinal tract, such as cholecystokinin whereas others may initiate meals, such as the recently discovered hormone, ghrelin. Other hormones such as insulin and leptin, together with circulating nutrients, indicate long-term energy stores. All these signals act at several central nervous system (CNS) sites but the pathways converge on the hypothalamus, which contains a large number of peptide and other neurotransmitters that influence food intake. As energy deficit is most likely to compromise survival, it is not surprising that the most powerful of these pathways are those that increase food intake and decrease energy expenditure when stores are depleted. When energy stores are low, production of leptin from adipose tissue, and thus circulating leptin concentrations fall, leading to increased production of hypothalamic neurotransmitters that strongly increase food intake, such as neuropeptide Y (NPY), galanin and agouti-related protein (AGRP) and decreased levels of alpha-melanocyte-stimulating hormone (alpha-MSH), cocaine and amphetamine-regulated transcript (CART) and neurotensin that reduce food intake and increase energy expenditure. The finding that mutations in leptin and POMC lead to severe early onset obesity in humans has highlighted the importance of these peptides in humans. This new understanding may eventually lead to new treatments for obesity that will be of particular benefit in the prevention and treatment of type 2 diabetes.
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PMID:Neuropeptides and appetite control. 1214 41

Ghrelin is a recently recognized gut-brain peptide originally derived from the gastric mucosa. It stimulates growth hormone release, increases appetite and facilitates fat storage, and may interact with glucose metabolism. We studied the ghrelin gene in a group of 70 tall and obese children (mean age 9.4 year, Z body mass index [BMI] and Z height >3 and/or BMI percentile >99%). We found 10 single nucleotide polymorphisms. One common polymorphism of the ghrelin gene, which corresponds to an amino acid change in the tail of the prepro-ghrelin molecule, was significantly associated with children with a higher BMI (P = 0.001), and with lower insulin secretion during the first part of an oral glucose tolerance test (P = 0.05) although no difference in glucose levels was noted. This might suggest increased insulin sensitivity, although this is not supported by the lack of difference in fasting and 2 hour insulin levels; alternatively, this may be indicative of impaired first phase insulin secretion. These data suggest that variations in the ghrelin gene contribute to obesity in children and may modulate glucose-induced insulin secretion.
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PMID:A variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children. 1216 52

Ghrelin is an acylated peptide, whose lipid modification is essential for its biological activities. Previous studies demonstrated that it strongly stimulates GH release and has a potent orexigenic action. Meanwhile, there is enough evidence showing that feeding states influence plasma ghrelin levels. Fasting stimulates ghrelin secretion, and feeding reduces plasma ghrelin levels. In this study we examined the regulation of plasma ghrelin by fasting in genetically obese animals considering its molecular forms. Plasma levels of active form of ghrelin as well as those of total ghrelin were reduced in ob/ob and db/db mice compared with those in their control mice. Zucker fatty (fa/fa) rats also showed lower plasma ghrelin levels by fasting than the control rats. Insulin-induced hypoglycemia, however, stimulated ghrelin secretion in the fasted fatty rats. Moreover, glucose injection was revealed to reduce plasma ghrelin levels in rats. The effect of the severity of obesity on secretory regulation of ghrelin was also studied. Older fatty rats showed low plasma ghrelin levels even after 48-h fasting. These data suggest that the short-term secretory regulation of total ghrelin and the active form of ghrelin is delayed in obese animals and that blood glucose levels may be involved in the delayed regulation.
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PMID:Delayed short-term secretory regulation of ghrelin in obese animals: evidenced by a specific RIA for the active form of ghrelin. 1219 46

The adage 'we are what we eat' is taking on a new meaning in our well-fed and increasingly sedentary culture, as many of us convert much of our excess food into body fat; in the USA, 60% of the population is now considered to be overweight. Obesity brings with it an increased risk of developing type II diabetes, hypertension and heart disease, so the mechanisms that control food intake and body weight are of considerable importance for public health and clinical medicine. The mass of body fat is now known to be regulated by several hormones and neuropeptides. Two of these, the circulating peptide hormones leptin and ghrelin have actions that include reciprocal effects on appetite-regulating neurons in the hypothalamus. This article reviews data discussed at a recent meeting(1), where an overview of recent developments in research into leptin and ghrelin was presented. Topics covered are the roles of leptin and ghrelin in the regulation of food intake and energy production; the integration of food intake with other energy-regulated processes, such as growth, sexual maturation and reproduction, sleep and the immune response; and pathological conditions, ranging from diabetes to psychiatric disorders.1 This report summarizes conclusions of the meeting 'Brain Somatic Cross-Talk and the Central Metabolism' held in Paris on January 28, 2002.
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PMID:Weight in the balance. 1221 45

Ghrelin, a novel endogenous ligand for the GH secretagogue receptor, has been reported to stimulate GH secretion and food intake in both humans and other animals. Interestingly, recent data indicate that ghrelin is up- and down-regulated in anorexia nervosa (AN) and obesity, which are also known to be accompanied by increased and reduced GH levels respectively. Ageing is associated with a gradual but progressive reduction in GH secretion, and by alterations in appetite and food intake. The role of ghrelin in the decline of somatotroph function and the anorexia of ageing is unknown. To investigate the influence of age on circulating levels of ghrelin, a total of 19 young and old normal weight subjects (Y-NW, n=12; O-NW, n=7), six patients with active AN (A-AN), and seven patients with morbid obesity (OB) were studied. In addition to fasting plasma ghrelin concentrations, baseline serum TSH, IGF-I and insulin levels were measured. Mean plasma ghrelin concentrations in A-AN or OB were higher and lower respectively than those present in Y-NW. Interestingly, mean plasma ghrelin concentrations in O-NW were significantly lower than those present in Y-NW and superimposable on those of OB. The mean fasting plasma ghrelin concentrations in all groups of subjects were negatively correlated with body mass index and serum insulin levels, but not with TSH and IGF-I levels. This study provides evidence of an age-related decline of plasma ghrelin concentrations, which might explain, at least partially, the somatotroph dysregulation and the anorexia of the elderly subject.
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PMID:Plasma ghrelin concentrations in elderly subjects: comparison with anorexic and obese patients. 1237 12

Ghrelin is a hormone produced by endocrine cells in the stomach. Ghrelin stimulates the secretion of growth hormone by the anterior pituitary. This effect is mediated by hypothalamic growth-hormone secretagogue receptors. Binding to these receptors not only stimulates growth hormone secretion, but also has vascular effects (positive inotropic effects), modifies (decreases) insulin sensitivity, affects glucose metabolism (hyperglycaemia) and stimulates gastric-acid production. Antiproliferative effects of ghrelin have been described on experimental tumour models. Ghrelin seems to play a role in stimulating the appetite as well as promoting a more effective storage of food components. Whether or not ghrelin could play any role in the induction of weight gain has yet to be established. This is also true for the role of potential ghrelin antagonists in the induction of weight loss in case of obesity.
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PMID:[Ghrelin, an important hormone produced by the stomach]. 1240 7

Obesity has become a leading public health concern. Over 1 billion people are now overweight or obese, and the prevalence of these conditions is rising rapidly. Remarkable new insights into the mechanisms that control body weight are providing an increasingly detailed framework for a better understanding of obesity pathogenesis. Key peripheral signals, such as leptin, insulin, and ghrelin, have been linked to hypothalamic neuropeptide systems, and the anatomic and functional networks that integrate these systems have begun to be elucidated. This article highlights some of these recent findings and their implications for the future of obesity treatment.
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PMID:Genetics and pathophysiology of human obesity. 1241 15

Ghrelin is a novel growth hormone-releasing peptide isolated from human and rat stomach that induces weight gain by increasing food intake and reducing fat utilization. Although recent data indicate that ghrelin is downregulated in human adult obesity, the characteristics of human obesity are heterogeneous, especially in children and adolescents, and depend on the distribution of subcutaneous and visceral fat tissue. We measured fasting plasma ghrelin concentrations by radioimmunoassay in 49 obese Japanese children and adolescents (38 boys and 11 girls; mean age 10.2 +/- 2.8 years; BMI 28.0 +/- 4.5 kg/m(2), percent overweight 56.0 +/- 20.7%), and analyzed associations of their ghrelin concentrations with their body composition, insulin resistance, and adipocytokine concentrations. Fasting plasma ghrelin levels were negatively correlated with BMI and waist circumference, but not with percent overweight or percent body fat, whereas fasting leptin levels were positively correlated with all of the following parameters: BMI, waist circumference, percent overweight, and percent body fat. Plasma ghrelin levels were negatively correlated with fasting immunoreactive insulin, homeostasis model assessment insulin resistance index, and quantitative insulin sensitivity check index values. There was no correlation between plasma ghrelin and leptin, but ghrelin was negatively correlated with the PAI-1 concentrations. The results suggest that the downregulation of ghrelin secretion may be a consequence of higher insulin resistance associated with visceral fat accumulation and elevated PAI-1 concentrations, and not a consequence of total body fat accumulation associated with elevated leptin concentrations.
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PMID:Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin, in obese children and adolescents. 1245 93

Prader-Willi syndrome (PWS) is a genetic disorder occurring in 1 of 10,000-16,000 live births and is characterized by excessive appetite with progressive massive obesity as well as short stature and mental retardation. Most patients have GH deficiency and hypogonadotropic hypogonadism. The causes of the hyperphagia and abnormal GH secretion are unknown. To determine whether ghrelin, a novel GH secretagogue with orexigenic properties, is elevated in PWS, we measured fasting plasma ghrelin concentration; body composition (dual-energy x-ray absorptiometry); and subjective ratings of hunger (visual analog scale) in seven subjects (6 males and 1 female; age, 26 +/- 7 yr; body fat, 39 +/- 11%, mean +/- SD) with PWS (diagnosis confirmed by genetic test) and 30 healthy subjects (reference population, 15 males and 15 females; age, 32 +/- 7 yr; body fat, 36 +/- 11%) fasted overnight. All subjects were weight stable for at least 6 months before admission to the study. The mean plasma ghrelin concentration was higher in PWS than in the reference population (307 +/- 164 vs. 109 +/- 24 fmol/ml; P < 0.001), and this difference remained significant after adjustment for percentage body fat (P < 0.001). Plasma ghrelin was also higher (P = 0.0004) in PWS than in five healthy subjects fasted for 36 h. A positive correlation was found between plasma ghrelin and subjective ratings of hunger (r = 0.71; P = 0.008). Furthermore, in subjects with PWS, the concentration of the hormone was not different before and after ingestion of 2 ml and a satiating amount of the same liquid meal (ghrelin concentrations: 307 +/- 164 vs. 306 +/- 205 vs. 260 +/- 134 fmol/ml, respectively; ANOVA for repeated measures, P = 0.56). This is the first evidence that ghrelin, a novel orexigenic hormone, is elevated in subjects with PWS. Our finding suggests that ghrelin may be responsible, at least in part, for the hyperphagia observed in PWS.
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PMID:High circulating ghrelin: a potential cause for hyperphagia and obesity in prader-willi syndrome. 1246 37


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