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

In addition to its orexigenic properties, ghrelin has been shown to modulate the secretory pattern of pituitary hormones, and it may exert direct effects on peripheral organs such as the gonads and endocrine pancreas. To study possible interactions among ghrelin, glucose homeostasis, and the reproductive system, we investigated 10 obese women with polycystic ovary syndrome (OB-PCOS) in comparison with 10 age- and body mass index-matched obese subjects (OB). Plasma levels of insulin, glucose, androgens, and ghrelin were measured at baseline condition and after 7 months of therapy (hypocaloric diet + metformin or placebo). Plasma ghrelin levels were lower in OB-PCOS than in OB (P < 0.05). A strong negative correlation between ghrelin and androstenedione levels was found in both populations at baseline (OB-PCOS: P < 0.01; OB: P < 0.001) and after therapy (OB-PCOS: P < 0.01; OB: P < 0.05), whereas no correlation was found between ghrelin and other androgens. In both groups, the markers of insulin resistance in fasting and stimulated conditions (glucose/insulin ratio, homeostasis model insulin resistance index, homeostasis model applied to the oral glucose tolerance test) demonstrated decreased insulin sensitivity. However, a negative correlation between plasma ghrelin and all these markers was observed only in the OB-PCOS group (P < 0.05). Accordingly, a negative correlation between ghrelin variation and treatment-induced changes of the glucose/insulin ratio, HOMA-R, and HOMA(OGTT) was observed only in the OB-PCOS group (P < 0.05). In conclusion, OB-PCOS women have lower ghrelin levels than those expected based on the presence of obesity. Only in OB-PCOS, ghrelin negatively correlates with insulin sensitivity. In addition, regardless of the presence of PCOS, a marked negative correlation exists between ghrelin and androstenedione levels, suggestive of an interaction between ghrelin and steroid synthesis or action.
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PMID:Plasma ghrelin, obesity, and the polycystic ovary syndrome: correlation with insulin resistance and androgen levels. 1246 63

Wide ranges in postnatal weight gain are seen in infants born small for gestational age (SGA); most show some catch-up growth and this may be driven by increased appetite. Ghrelin, the natural ligand of the GH secretagogue receptor, has potent orexigenic effects. In adults circulating ghrelin levels are increased in anorexia, decreased in obesity and show post prandial suppression. The aim of the present study was to test the hypothesis that rate of weight gain over the first year in SGA infants may relate to variable suppression of circulating ghrelin levels. Serum ghrelin levels were measured in 1 y old infants born SGA (n = 85) and in control infants born adequate for gestatitional age (AGA) (n = 22) fasting and 10 minutes after intravenous (iv) glucose (0.5 g/Kg of 25% dextrose). Sex- and gestational age-adjusted SD scores (SDS) for body weight were calculated at birth and at 1 y, and delta weight SDS between 0-1 y was calculated as an index of postnatal weight gain. In both SGA and AGA groups, ghrelin levels reduced from fasting (mean +/- SE: 104.4 +/- 6.4 fmol/ml) to 10 minutes post-iv glucose (82.7 +/- 5.3, p < 0.005). There were no differences in ghrelin levels between SGA and AGA infants (fasting or post-iv glucose). However, in SGA infants ghrelin levels post-glucose, but not fasting, were psitively related to current length (r = 0.28, p < 0.05), weight (r = 0.23, p < 0.05) and to change in weight SDS 0-1 y (r = 0.22, p < 0.05). SGA infants who showed poor catch-up growth showed a larger decline in ghrelin concentrations post-iv glucose. In conclusion, circulating ghrelin levels rapidly decreased after iv glucose. Higher ghrelin levels or lower reductions in circulating levels following iv glucose were seen in SGA infants who showed greater infancy weight gain, suggesting that sustained orexigenic drive could contribute to postnatal catch-up growth.
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PMID:Fasting and post-glucose ghrelin levels in SGA infants: relationships with size and weight gain at one year of age. 1246 94

The co-ordinated regulation of food intake and energy expenditure takes place in the hypothalamic regions of the brain. Current understanding of the systems involved in this regulation suggests that, in the hypothalamus, there are two major groups of neuropeptides involved in orexigenic and anorexic processes. The orexigenic neuropeptides are neuropeptide Y (NPY) and agouti-related peptide (AgRP) and the anorexic neuropeptides are alpha-melanocyte-stimulating hormone (alpha-MSH) and cocaine and amphetamine-related transcript (CART). Theneurons expressing these neuropeptides interact with each other and with signals from the periphery (such as leptin, insulin, ghrelin and glucocorticoids) to regulate feeding behaviour, energy expenditure and various endocrine axes. Although direct evidence is limited, there are examples of genetic obesity in humans which suggest that the balance between orexigenic and anorexic pathways in the hypothalamus is also pivotally important in the maintenance of energy homeostasis in humans.
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PMID:Hypothalamic regulation of energy homeostasis. 1246 11

Ghrelin, an endogenous ligand of the GH secretagogue receptor, stimulates appetite and causes obesity in animal models and in humans when given in pharmacologic doses. Prader-Willi Syndrome (PWS) is a genetic obesity syndrome characterized by GH deficiency and the onset of a voracious appetite and obesity in childhood. We, therefore, hypothesized that ghrelin levels may play a role in the expression of obesity in this syndrome. We measured fasting serum ghrelin levels in 13 PWS children with an average age of 9.5 yr (range, 5-15) and body mass index (BMI) of 31.3 kg/m2 (range, 22-46). The PWS group was compared with 4 control groups: 20 normal weight controls matched for age and sex, 17 obese children (OC), and 14 children with melanocortin-4 receptor mutations (MC4) matched for age, sex, and BMI, and a group of 3 children with leptin deficiency (OB). In non-PWS subjects, ghrelin levels were inversely correlated with age (r = 0.36, P = 0.007), insulin (r = 0.55, P < 0.001), and BMI (r = 0.62, P < 0.001), but not leptin. In children with PWS, fasting ghrelin concentrations were not significantly different compared with normal weight controls (mean +/- SD; 429 +/- 374 vs. 270 +/- 102 pmol/liter; P = 0.14). However, children with PWS did demonstrate higher fasting ghrelin concentrations (3- to 4-fold elevation) compared with all obese groups (OC, MC4, OB) (mean +/- SD; 429 +/- 374 vs. 139 +/- 70 pmol/liter; P < 0.001). In conclusion, ghrelin levels in children with PWS are significantly elevated (3- to 4-fold) compared with BMI-matched obese controls (OC, MC4, OB). Elevation of serum ghrelin levels to the degree documented in this study may play a role as an orexigenic factor driving the insatiable appetite and obesity found in PWS.
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PMID:Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome. 1251 48

The hypothalamus integrates metabolic, neural and hormonal signals to evoke an intermittent appetitive drive in the daily management of energy homeostasis. Three major players identified recently in the feedback communication between the periphery and hypothalamus are leptin, ghrelin and neuropeptide Y (NPY). We propose that reciprocal circadian and ultradian rhythmicities in the afferent humoral signals, anorexigenic leptin from adipocytes and orexigenic ghrelin from stomach, encode a corresponding discharge pattern in the appetite-stimulating neuropeptide Y network in the hypothalamus. An exquisitely intricate temporal relationship among these signaling modalities with varied sites of origin is paramount in sustenance of weight control on a daily basis. Our model envisages that subtle and progressive derangements in temporal communication, imposed by environmental shifts in energy intake, impel a positive energy balance culminating in excessive weight gain and obesity. This conceptual advance provides a new target for designing pharmacologic or gene transfer therapies that would normalize the rhythmic patterns of afferent hormonal and efferent neurochemical messages.
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PMID:Rhythmic, reciprocal ghrelin and leptin signaling: new insight in the development of obesity. 1260 43

The stomach-derived peptide, ghrelin, has recently been discovered as an important regulator of energy homeostasis. Central nervous system pathways involving stimulation of hypothalamic neuropeptides play a prominent role in mediating ghrelin's orexigenic effects. However, potential direct peripheral effects remain poorly understood. Using a brown adipocyte model, we tested ghrelin-mediated influences on adipose tissue. Chronic ghrelin stimulation of differentiating adipocytes did not affect the pattern or extent of fat accumulation. Furthermore, insulin-induced glucose uptake as a hallmark of adipocyte function was not altered by ghrelin pre-treatment. However, acute ghrelin treatment resulted in a significant time-dependent increase in p44/42 mitogen-activated protein kinase phosphorylation. There was no stimulation of phosphatidylinositol 3-kinase, JAK/STAT, or stress kinase signaling pathways. Furthermore, ghrelin did not significantly alter gene expression of the thermogenic uncoupling protein-1. By contrast, expression of the novel adipokine adiponectin, which has been implicated in the pathogenesis of insulin resistance and obesity, was strongly impaired. This inhibition occurred acutely, and was sustained for several hours. In summary, our data provide evidence for selective effects of ghrelin on adipocyte signaling and function and thus propose a role for adipose tissue as a novel mediator of ghrelin's effects on energy balance and glucose homeostasis.
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PMID:Direct peripheral effects of ghrelin include suppression of adiponectin expression. 1266 Aug 74

The novel peptide hormone ghrelin has recently been recognized as an important co-regulator of growth hormone secretion and energy homeostasis. The significance of ghrelin for obesity and cachexia as well as in the regulation of growth processes is the subject of ongoing basic research as well as clinical studies. It is our goal to emphasize the critical significance of the hypothalamic signaling modalities induced by ghrelin for a better understanding of how this novel hormone affects energy balance and metabolism.
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PMID:Ghrelin in hypothalamic regulation of energy balance. 1267 40

Adipocytal hormones resistin and adiponectin and gastric peptide ghrelin are recently discovered hormones, which are considered to take part in energy metabolism regulation. Resistin is expressed in adipose tissue only and its increased levels could cause insulin resistance and thus link obesity with type 2 diabetes. Adiponectin, as well as resistin, are products of genes, expressed in adipose tissue. Adiponectin could prevent development of aterosclerosis and it could play a role in anti-inflammatory reactions. Ghrelin is produced mainly in the stomach. Beside its role in long-term regulation of energy metabolism, it is involved in the short-term regulation of feeding. Main roles of resistin, adiponectin and ghrelin are summarised in the presented overview.
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PMID:[Recently discovered hormones with a role in energy homeostasis]. 1269 33

In order to develop an effective pharmacological treatment for obesity, an endogenous factor that promotes a positive energy balance by increasing appetite and decreasing fat oxidation could represent the drug target scientists have been looking for. The recently discovered gastric endocrine agent ghrelin, which appears to be the only potent hunger-inducing factor to naturally circulate in our blood stream, was discovered in 1999. Since then the acylated peptide hormone ghrelin has evolved from an endogenous growth hormone secretagogue to a regulator of energy balance to a pleiotropic hormone with multiple sources, numerous target tissues and most likely several physiological functions. Although neither the exact mechanism of action by which ghrelin increases food intake and adiposity is known, nor the putatively differential effects of brain-derived and stomach-derived ghrelin on energy homeostasis have been determined, blocking or neutralizing ghrelin action still seems one of the more reasonable pharmacological approaches to reverse a chronically positive energy balance. However, based on growing experience with compounds targeting the neuroendocrine regulation of energy balance, it is quite possible that a ghrelin antagonist will either fail to cure obesity due to the existence of compensatory mechanisms or undesired effects might reveal the true biological function of ghrelin (e.g. cardiovascular mechanisms, anti-proliferative effects, reproduction).
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PMID:Ghrelin as a potential anti-obesity target. 1276 30

Obesity is a growing epidemic, causally associated with a number of serious medical conditions, including diabetes mellitus, coronary heart disease, and several cancers. The gut hormones ghrelin and peptide YY are secreted from the gut in response to changes to nutritional status. While food intake is stimulated by ghrelin, it is inhibited by peptide YY. The discovery, anatomy, and physiology of ghrelin and peptide YY are discussed, focusing on the adaptive changes in diseases such as obesity and anorexia nervosa. Ghrelin and PYY are important therapeutic targets in the quest to find an effective antiobesity treatment.
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PMID:Gut and mind. 1280 49


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