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

In summary, available literature indicates that GH secretion is blunted profoundly in individuals with relative or absolute obesity. Accumulation of AVF particularly represses GH release. Administration of GH to obese adults decreases total body fat and especially AVF. Furthermore, GH supplementation combined with dietary restriction and/or exercise appears to enhance favorable changes in body composition. Although exercise is a powerful stimulus to GH release, the GH response to exercise is blunted in older and obese individuals. This suggests that higher relative exercise intensities may be necessary for exercise alone to stimulate adequate GH release in obese subjects. In as much as exercise in combination with a second stimulus of GH release (e.g. GHRP-2, L-arginine) drives GH release synergistically, we propose that combining exercise and a GH secretagogue may have utility in restoring GH release in obese adults. Taken as a whole, available data suggest that GH repletion regimens in combination with regular exercise and relevant dietary intervention may provide a tripartite strategy for the management of significant obesity.
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PMID:Body composition, physical exercise, growth hormone and obesity. 1170 5

Obese patients show marked impairment in spontaneous secretion as well as in the somatotroph responsiveness to all provocative stimuli. GH insufficiency in obese patients has been reported reversible after long-term diet and marked weight loss but somatotroph secretion is not restored by fasting. Among potential neuroendocrine causes, GHRH hypoactivity has been shown but it is likely that alterations in the influence of ghrelin, the gastric-derived natural ligand of the GHS-R, and or of the NPY/leptin interplay could have a role. Among metabolic alterations, the chronic elevation of FFA levels and hyperinsulinism probably have a key role in causing GH insufficiency in obesity. Despite marked GH insufficiency, total IGF-I levels are basically preserved while free IGF-I levels are even increased thus questioning real hypoactivity of GH/IGF-I axis in obesity. Peripheral GH hypersensitivity due to increased GH receptor status, hyperinsulinism and reduced IGFBP-I levels likely explain almost normal total IGF-I and increased free IGF-I levels which, in turn, probably exert an increased negative feedback action on somatotroph cells.
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PMID:Neuroendocrine and metabolic determinants of the adaptation of GH/IGF-I axis to obesity. 1199 78

GH secretion is regulated by hypothalamic and peripheral hormones under a very complex interplay. Superimposed on this regulation, signals of a metabolic nature connect GH secretion with the metabolic and energetic homeostasis of a given individual. GH secretion is enhanced in malnutrition and is severely impeded in obesity, but no information is available to explain why GH secretion is severely impeded or blocked in excess adiposity. Obesity is associated with high plasma levels of leptin, and leptin participates at the hypothalamic and pituitary levels in the regulation of GH secretion. Thus, it has been postulated that the inhibitory action of obesity on GH discharge may be mediated by excess leptin levels. The only situation in which obesity does not parallel leptin values is the rare case of morbid obesity due to leptin deficiency caused by missense mutation of the leptin gene. To understand the causes of GH blockade presented in obesity, patients with both homozygous and heterozygous mutations of the leptin gene and matched controls for both sex and body mass index (BMI) were studied. Three homozygous and 5 heterozygous patients with leptin gene mutations as well as 13 control subjects were studied. In all subjects basal levels of leptin and GH values stimulated by the combined administration of GHRH plus GH-releasing peptide-6 (GHRP-6) were analyzed. To analyze the effects of obesity and leptin levels, 5 groups were designed, all them matched by sex and adiposity. The number of subjects (n), leptin levels in micrograms per liter, and adiposity in BMI were as follows: nonobese subjects: n = 5, BMI = 22.1 +/- 0.9 kg/m2, leptin = 5.4 +/- 0.9; heterozygous patients: n = 5, BMI = 27.0 +/- 1.0 kg/m2, leptin = 2.3 +/- 0.1; controls for the heterozygous group: n = 5, BMI = 24.7 +/- 1.1 kg/m2, leptin = 5.7 +/- 1.2; homozygous patients: n = 3, BMI = 54.4 +/- 0.2 kg/m2, leptin = 1.0 +/- 0.2; and controls for the homozygous group: n = 3, BMI = 50.3 +/- 2.0 kg/m2, leptin = 35.0 +/- 6.6. In these matched groups, the GHRH- and GHRP-6-stimulated GH secretion (mean peak +/- SE; micrograms per liter) was: nonobese, 86.8 +/- 8.9 [significantly higher than heterozygous (28.6 +/- 4.9) and control for heterozygous (39.9 +/- 10.4)]; homozygous group, 9.4 +/- 3.0; control for homozygous, 9.3 +/- 1.0 (significantly lower than the heterozygous, control for heterozygous, and nonobese groups). Hence, it appeared that GH discharge was negatively conditioned by adiposity and was not influenced by leptin levels. To further analyze this observation, a correlation analysis showed that GH peaks were negatively correlated with BMI in the 13 control subjects as well as in the 8 leptin-deficient patients. On the contrary, the GH peaks were negatively correlated with leptin levels in controls, but showed the opposite pattern in homo- and heterozygous patients. In conclusion, the GH secretion blockade, which is characteristic of obese states, is due to adiposity or some factor linked to adiposity, but not to elevated plasma leptin levels.
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PMID:The inhibition of growth hormone secretion presented in obesity is not mediated by the high leptin levels: a study in human leptin deficiency patients. 1251 70

Controversial data were reported on GH response to different provocative stimuli in obese patients with polycystic ovary syndrome (PCOS). The objective of our study was to assess the effect of short-term fasting on GH response to combined stimulus with GHRH+GH-releasing peptide-6 (GHRP-6) in obese patients with PCOS and possible relation with leptin and insulin changes during fasting. Twelve obese PCOS women and nine obese control women participated in 3-day fasting. GH response, IGF-I, insulin and leptin were measured after GHRH+ GHRP-6, before and after short-term fasting. Obese PCOS patients had significantly greater GH peak after GHRH+GHRP-6 before fasting. Enhanced response to GH stimulation was found after fasting without substantial differences between obese PCOS and obese controls. Insulin and leptin significantly decreased, while insulin sensitivity significantly improved in both groups during fasting. In conclusion, obese PCOS patients have peculiar type of GH response to GHRH+GHRP-6 before fasting, possibly due to enhanced sensitivity of somatotrophs. Observed changes in insulin and leptin may participate in modulation of enhanced GH response after short-term fasting to GHRH+GHRP-6 in PCOS and obese controls.
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PMID:Growth-hormone response to combined stimulation with GHRH plus GH-releasing peptide-6 in obese patients with polycystic ovary syndrome before and after short-term fasting. 1284 41

Rats selectively bred to develop diet-induced obesity (DIO) spontaneously gain more body weight between 5 and 7 wk of age than do those bred to be diet resistant (DR). Here, chow-fed DIO rats ate 9% more and gained 19% more body weight from 5 to 6 wk of age than did DR rats but had comparable leptin and insulin levels. However, 6-wk-old DIO rats had 29% lower plasma ghrelin levels at dark onset but equivalent levels 6 h later compared with DR rats. When subsequently fed a high-energy (HE; 31% fat) diet for 10 days, DIO rats ate 70% more, gained more body and adipose depot weight, had higher leptin and insulin levels, and had 22% lower feed efficiency than DR rats fed HE diet. In DIO rats on HE diet, leptin levels increased significantly at 3 days followed by increased insulin levels at 7 days. These altered DIO leptin and ghrelin responses were associated with 10% lower leptin receptor mRNA expression in the arcuate (ARC), dorsomedial (DMN), and ventromedial hypothalamic nuclei and 13 and 15% lower ghrelin receptor (GHS-R) mRNA expression in the ARC and DMN than in the DR rats. These data suggest that increased ghrelin signaling is not a proximate cause of DIO, whereas reduced leptin sensitivity might play a causal role.
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PMID:Abnormalities of leptin and ghrelin regulation in obesity-prone juvenile rats. 1286 57

Ghrelin, a novel 28-amino acid orexigenic peptide discovered in 1999, has given us further insights into the control of energy homeostasis and growth hormone secretion. As a natural endogenous ligand of the growth hormone secretagogue receptor, it potently stimulates growth hormone release but is also implicated in many other homeostatic mechanisms. Released from the stomach, it stimulates lactotroph and corticotroph secretion, increases appetite and adiposity, has beneficial hemodynamic effects, has prokinetic and gastric acid secretory functions in the stomach, and may even be implicated in sleep. As advances in the understanding of appetite and obesity are made, it is timely to review the possibly central role of ghrelin in these physiological and pathophysiological states. This review will discuss the recent literature concerning this exciting novel neuropeptide and discuss the possible therapeutic possibilities it may open up to us.
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PMID:Ghrelin for the gastroenterologist: history and potential. 1459 66

Ghrelin is a 28-amino-acid peptide predominantly produced by the stomach, while substantially lower amounts derive from other tissues including the pancreas. It is a natural ligand of the GH secretagogue (GHS) receptor (GHS-R1a) and strongly stimulates GH secretion, but acylation in serine 3 is needed for its activity. Ghrelin also possesses other endocrine and nonendocrine actions reflecting central and peripheral GHS-R distribution including the pancreas. The wide spectrum of ghrelin activities includes orexigenic effect, control of energy expenditure, and peripheral gastroenteropancreatic actions. Circulating ghrelin levels mostly reflect gastric secretion as indicated by evidence that they are reduced by 80% after gastrectomy and even after gastric by-pass surgery. Ghrelin secretion is increased in anorexia and cachexia but reduced in obesity, a notable exception being Prader-Willi syndrome. The negative association between ghrelin secretion and body weight is emphasized by evidence that weight increase and decrease reduces and augments circulating ghrelin levels in anorexia and obesity, respectively, and agrees with the clear negative association between ghrelin and insulin levels. In fact, ghrelin secretion is increased by fasting whereas it is decreased by glucose load as well as during euglycemic clamp but not after arginine or free fatty acid load in normal subjects; in physiological conditions, however, the most remarkable inhibitory input on ghrelin secretion is represented by somatostatin as well as by its natural analog cortistatin that concomitantly reduce beta-cell secretion. This evidence indicates that the endocrine pancreas plays a role in directly or indirectly modulating ghrelin secretion.
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PMID:Ghrelin and the endocrine pancreas. 1461 Feb 95

GH secretagogue receptor (GHSR, ghrelin receptor) is involved in regulation of body weight and GH secretion. We initially analyzed two single-nucleotide polymorphisms of the GHSR in up to 184 extremely obese children and adolescents and up to 184 healthy underweight students. The frequency of the 171T allele of rs495225 was higher in our obese samples (75.0%) than in the underweight individuals (70.2%; nominal P = 0.14). This trend could not be substantiated in an additional association study in 270 obese and 145 underweight and normal weight individuals and in a transmission disequilibrium test based on 387 obesity trios (transmission rate of 171T, 51.8%; nominal P = 0.53). Additionally, the coding region of GHSR was systematically screened, and seven sequence variants were identified in 93 obese, 96 normal weight, and 94 underweight individuals and 43 children with short normal stature (SNS). Five silent single-nucleotide polymorphisms showed similar genotype frequencies in the different weight groups and SNS children (all nominal P > 0.3). Two novel missense variants were detected only in one obese carrier and one SNS child, respectively. In conclusion, we did not obtain conclusive evidence for an involvement of the ghrelin receptor gene in body weight regulation or SNS in our study groups.
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PMID:Ghrelin receptor gene: identification of several sequence variants in extremely obese children and adolescents, healthy normal-weight and underweight students, and children with short normal stature. 1471 43

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

Polycystic ovary syndrome is a common endocrine disorder in women. It is associated with hirsuitism, obesity, insulin resistance, abnormality in the growth hormone/insulin-like growth factor I (IGF-1) axis and polycystic ovaries. The etiology of PCOS has not been clarified. Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor. It is mainly secreted by stomach cells but has also been shown to be present in hypothalamus, pituitary, pancreas and gonads. Ghrelin is a regulator of energy homeostasis and GH secretion. The influence of ghrelin on insulin secretion and gonadal function is known. Since ghrelin may play an important role in pathophysiology of PCOS, we studied ghrelin levels in a group of 52 women with PCOS and in 16 women in a control group. Plasma levels of insulin, total testosterone, SHBG, LH, and FSH were also measured. In conclusion, PCOS women have higher ghrelin levels than controls. Ghrelin negatively correlates with BMI and insulin levels in PCOS group. A relation between ghrelin and SHBG was observed. Our data suggest that ghrelin could be the possible link in PCOS etiology.
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PMID:Elevated ghrelin plasma levels in patients with polycystic ovary syndrome. 1548 19


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