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

Ghrelin plays a key role in the regulation of growth hormone secretion and energy homeostasis. Adiponectin is exclusively secreted by adipose tissue and is abundantly present in the circulation, with important effects on metabolism. We studied five lean and five obese young men [ages: 24.2 +/- 1.0 (lean) and 21.8 +/- 1.6 (obese) years (difference not significant); body mass indexes: 35.0 +/- 1.3 and 23.0 +/- 0.3 kg/m2 (P = 0.01)], sampled blood every 7 min over 24 h, and measured ghrelin, adiponectin, and leptin in 2,070 samples for a total of 6,210 data points. Circulating 24-h ghrelin showed significant ultradian fluctuations and an orderly pattern of release in lean and obese subjects with similar pulsatility characteristics. Plasma adiponectin concentrations were significantly lower in the obese group, with lower pulse height. In contrast to leptin, which is secreted in an orderly manner, the 24-h patterns of adiponectin were not significantly different from random in both the lean and obese groups. We show here that adipocytes can simultaneously secrete certain hormones, such as leptin, in patterns that are orderly, whereas other hormones, such as adiponectin, are secreted in patterns that appear to be random. The cross-approximate entropy statistic revealed pattern synchrony among ghrelin-leptin, ghrelin-adiponectin, and leptin-adiponectin hormone time series in the lean and obese subjects. Plasma ghrelin concentrations showed a nocturnal rise that exceeded the meal-associated increases in lean subjects, and this newly identified nocturnal rise was blunted in the obese. We suggest that the blunting of the nocturnal rise of ghrelin is a biological feature of human obesity.
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PMID:Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity. 1523 97

Binge eating disorder (BED), characterized by ingestion of very large meals without purging afterwards, is found in a subset of obese individuals. We showed previously that stomach capacity is greater in obese than in lean subjects, and in this study, we investigated capacity in obese individuals with BED. We also determined ad-libitum intake of a test meal until extremely full. Furthermore, we measured various appetitive hormones (insulin, leptin, glucagon, CCK, ghrelin) and glucose before a fixed meal and for 120 min afterwards. An acetaminophen tracer was used to assess gastric emptying rate. We compared three groups of overweight women: 11 BED, 13 BE (subthreshold BED), and 13 non-binge-eating normals. The BED individuals had the largest stomach capacity as assessed by either maximum volume tolerated (P=.05) or by gastric compliance to pressure (P=.02) using an intragastric balloon. Although test meal intake did not differ between groups, it correlated (P=.03) with gastric capacity. The BED group showed a tendency (P=.06) to have greater area under the curve (AUC) and had higher values at 5 and 60 min (P<.05) for insulin compared to normals. Moreover, the BED subjects had lower ghrelin baselines premeal, and lower AUC for ghrelin, which then declined less postmeal than for the normals (P<.05). None of the other blood values differed, including glucose, leptin glucagon, and CCK, as well as acetaminophen, reflecting gastric emptying. The lower ghrelin in BED, although contrary to what was expected, is consistent with lower ghrelin in obesity, and suggests down-regulation of ghrelin by overeating. The lack of differences in CCK is consistent with the lack of differences in gastric emptying rate, given that CCK is released when nutrients reach the intestine. The results show that BED subjects have a large gastric capacity as well as abnormalities in meal-related ghrelin and insulin patterns that may be factors in binge eating.
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PMID:Gastric capacity, test meal intake, and appetitive hormones in binge eating disorder. 1523 78

Polycystic ovary syndrome (PCOS) is a common endocrine condition in women of reproductive age associated with obesity. It may involve dysregulation of ghrelin, a hormone implicated in appetite regulation. The effect of diet composition on ghrelin is unclear. Overweight women with and without PCOS were randomized to a high-protein (40% carbohydrate, 30% protein; 10 PCOS, six non-PCOS) or standard protein diet (55% carbohydrate, 15% protein; 10 PCOS, six non-PCOS) for 12 wk of energy restriction and 4 wk of weight maintenance. Diet composition had no effect on fasting or postprandial ghrelin or measures of satiety. Non-PCOS subjects had a 70% higher fasting baseline ghrelin (P = 0.011), greater increase in fasting ghrelin (57.5 vs. 34.0%, P = 0.033), and greater maximal decrease in postprandial ghrelin after weight loss (-144.1 +/- 58.4 vs. -28.9 +/- 14.2 pg/ml, P = 0.02) than subjects with PCOS. Subjects with PCOS were less satiated (P = 0.001) and more hungry (P = 0.007) after a test meal at wk 0 and 16 than subjects without PCOS. Appetite regulation, as measured by subjective short-term hunger and satiety and ghrelin homeostasis, may be impaired in PCOS.
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PMID:Ghrelin and measures of satiety are altered in polycystic ovary syndrome but not differentially affected by diet composition. 1524 Jun 12

Ghrelin is a GH-releasing acylated peptide found in the stomach and a centrally acting food intake stimulator. Prader-Willi syndrome (PWS) is a genetic disorder characterized by a voracious appetite and increased fasting ghrelin levels. In this report we describe 24-h ghrelin profiles in PWS children (n = 5) and compare these with age, sex, and body mass index (BMI)-matched controls (n = 5). A 3- to 4-fold increase in ghrelin levels was found in PWS over a 24-h period, compared with controls (P < 0.001). Interestingly, there was a greater tendency for the up-regulation of ghrelin level in lean PWS than in obese PWS. To confirm this finding, we measured fasting ghrelin levels in 39 patients with PWS. Inverse correlations were found between plasma ghrelin levels and the following: age (r = -0.408, P = 0.005), BMI (r = -0.341, P = 0.017), percentage of the ideal weight for age (r = -0.382, P = 0.008), and BMI percentile (r = -0.311, P = 0.027). Our data show that there may be a suppressive (or up-regulating) controlling mechanism of ghrelin secretion in obese (or lean) PWS children. We hope that our data may further explain the mechanisms underlying the insatiable appetite and obesity characteristic of PWS.
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PMID:Correlation between fasting plasma ghrelin levels and age, body mass index (BMI), BMI percentiles, and 24-hour plasma ghrelin profiles in Prader-Willi syndrome. 1529 22

Patients with phenylketonuria (PKU) have a diet-controlled deficiency in the conversion of phenylalanine (Phe) to tyrosine (Tyr), leading to decreased production of noradrenaline, adrenaline, and dopamine. Poor diet control results in high plasma Phe and low plasma Tyr and catecholamine concentrations. Ghrelin, a recently described gastrointestinal hormone that is elevated in the fasting state and low in the fed state, is considered a major appetite-stimulating hormone, possibly involved in the generation of obesity and insulin resistance. We evaluated morning preprandial plasma ghrelin levels in 14 diet-controlled and 15 poorly controlled PKU patients and 20 age- and body mass index (BMI)-matched healthy children (controls) and correlated its concentrations with those of Phe and catecholamines as well as with their BMI and 24-h nutrient intake. Plasma ghrelin levels were measured by RIA, plasma catecholamine concentrations were determined by HPLC with electrochemical detection, and Phe and Tyr levels were measured in an amino acid analyzer. The ghrelin concentration (744 +/- 25 ng/liter) in diet-controlled patients did not differ from that in controls (802 +/- 26 ng/liter; P > 0.05). On the contrary, the ghrelin concentration was significantly reduced in poorly controlled patients (353 +/- 23 ng/liter; P < 0.0001). Ghrelin correlated negatively with Phe in all three groups, whereas it correlated positively with catecholamine levels and energy intake and negatively with BMI only in diet-controlled patients and controls. We conclude that ghrelin secretion may receive positive direct or indirect input from catecholamines. The absence of a correlation between ghrelin and catecholamines, energy intake, or BMI in PKU patients on an inadequate diet may be due to dysregulation of their neuroendocrine system and might be affected by high Phe levels in the stomach and/or central nervous system.
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PMID:Morning preprandial plasma ghrelin and catecholamine concentrations in patients with phenylketonuria and normal controls: evidence for catecholamine-mediated ghrelin regulation. 1529 37

Prader-Willi syndrome (PWS) is characterized by life-threatening childhood-onset hyperphagia, obesity and, uniquely, high plasma levels of ghrelin, the orexigenic gastric hormone. Somatostatin suppresses ghrelin secretion in normal subjects. We therefore examined the effect of somatostatin on plasma ghrelin and appetite in four male PWS adults fasted overnight in a double-blind, placebo-controlled, randomized cross-over study. Subjects received an intravenous infusion of somatostatin (250 microg/hr) or saline for 300 min, and had blood samples taken every 30 min for measurement of plasma ghrelin and PYY3-36 (anorexigenic intestinal hormone) by radio-immunoassay, and glucose. Appetite was measured by counting sandwiches eaten over a 60 min free food access period from +120 min. Despite somatostatin lowering fasting plasma ghrelin by 60 +/- 2% (P = 0.04) to levels seen in non-PWS men, there was no associated reduction in food intake (105 +/- 9% of food intake during saline infusion, P = 0.6). Somatostatin also lowered plasma PYY levels by 45 +/- 16% (P = 0.04), and produced post-prandial hyperglycemia (P = 0.04). We conclude that either hyperghrelinemia may not contribute to hyperphagia in PWS adults, or perhaps concomitant reductions in anorexigenic gastrointestinal hormones by somatostatin counteracted any anorexigenic effect of lowering orexigenic ghrelin. Somatostatin analogues may therefore not be an effective therapy for obesity in PWS. Larger chronic studies with long-acting somatostatin analogues will be needed to determine their benefits and risks in treating PWS obesity.
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PMID:Somatostatin infusion lowers plasma ghrelin without reducing appetite in adults with Prader-Willi syndrome. 1529 65

The degree of nutrient enhancement during the newborn period may modulate programming of appetite-regulating hormones, body composition, and propensity to adult obesity in intrauterine growth-restricted (IUGR) newborns. Pregnant rats received, from day 10 to term gestation and throughout lactation, ad libitum food (AdLib) or 50% food restriction (FR) to produce IUGR newborns. AdLib vs. FR offspring were studied at day 1, and, to create two distinct groups of newborn catch-up growth (immediate, delayed) among the IUGR newborns, cross-fostering techniques were employed. The four groups of pups at 3 wk were IUGR immediate catch-up growth (FR/AdLib), IUGR delayed catch-up growth (FR/FR), control (AdLib/AdLib), and lactation FR control (AdLib/FR). From 3 wk to 9 mo, all offspring had AdLib rat chow. Maternal FR during pregnancy resulted in IUGR pups (6.0 +/- 0.3 vs. 7.1 +/- 0.3 g, P < 0.01) with decreased leptin (0.66 +/- 0.03 vs. 1.63 +/- 0.12 ng/ml, P < 0.001) and increased ghrelin (0.43 +/- 0.03 vs. 0.26 +/- 0.02 ng/ml, P < 0.001). Maternal FR during lactation (FR/FR) further impaired IUGR offspring growth at 3 wk. However, by 9 mo, these pups attained normal body weight, percent body fat, and plasma leptin levels. Conversely, IUGR offspring nursed by AdLib dams (FR/AdLib) exhibited rapid catch-up growth at 3 wk and continued accelerated growth, resulting in increased weight, percent body fat, and plasma leptin levels. Thus the degree of newborn nutrient enhancement and timing of IUGR newborn catch-up growth may determine the programming of orexigenic hormones and offspring obesity.
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PMID:Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition. 1529 66

Ghrelin is a novel orexigenic peptide hormone. In humans and rodents, it increases food intake and its levels are reduced in obesity but increased in fasting. It is an antagonistic signal to leptin informing the central nervous system about negative energy balance. The tundra vole (Microtus oeconomus) is an interesting model to study the effects of ghrelin, as it is poorly adapted to fasting. In this study, 10 male voles were injected with intraperitoneal ghrelin at 10 microg kg(-1)day(-1) for four days, while 10 males received sham injections. Additional five males were food deprived for 4 h with five males as fed controls. Exogenous ghrelin caused an expected elevation in the plasma ghrelin concentrations. Furthermore, the plasma glucose and high density lipoprotein cholesterol concentrations increased but the kidney and muscle glycogen contents decreased. The liver lipase and kidney glycogen phosphorylase activities increased at the same time. Food deprivation caused an increase in the plasma ghrelin concentrations. In voles, ghrelin may be a mediator to recruit body energy reserves during negative energy balance that would be detrimental to voles very rapidly if foraging does not prove to be successful.
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PMID:Effects of peripheral ghrelin on the carbohydrate and lipid metabolism of the tundra vole (Microtus oeconomus). 1530 67

Neuropeptide Y is the most potent physiological appetite transducer known. The NPY network is the conductor of the hypothalamic appetite regulating orchestra in the arcuate nucleus-paraventricular nucleus (ARC-PVN) of the hypothalamus. NPY and cohorts, AgrP, GABA and adrenergic transmitters, initiate appetitive drive directly through Y1, Y5, GABAA and alpha1 receptors, co-expressed in the magnocellular PVN (mPVN) and ARC neurons and by simultaneously repressing anorexigenic melanocortin signaling in the ARC-PVN axis. The circadian and ultradian rhythmicities in NPY secretion imprint the daily circadian and episodic feeding patterns. Although a number of afferent hormonal signals from the periphery can directly modulate NPYergic signaling, the reciprocal circadian and ultradian rhythmicities of anorexigenic leptin from adipocytes and orexigenic ghrelin from stomach, encode a corresponding pattern of NPY discharge for daily meal patterning. Subtle and progressive derangements produced by environmental and genetic factors in this exquisitely intricate temporal relationship between the two opposing humoral signals and the NPY network promote hyperphagia and abnormal rate of weight gain culminating in obesity and attendant metabolic disorders. Newer insights at cellular and molecular levels demonstrate that a breakdown of the integrated circuit due both to high and low abundance of NPY at target sites, underlies hyperphagia and increased adiposity. Consequently, interruption of NPYergic signaling at a single locus with NPY receptor antagonists may not be the most efficacious therapy to suppress hyperphagia and obesity. Central leptin gene therapy in rodents has been shown to subjugate, i.e. bring under homeostatic control, NPYergic signaling and suppress the age-related and dietary obesity for extended periods and thus shows promise as a newer treatment modality to curb the pandemic of obesity and metabolic syndrome.
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PMID:NPY and cohorts in regulating appetite, obesity and metabolic syndrome: beneficial effects of gene therapy. 1533 72

Public health efforts and current antiobesity agents have not controlled the increasing epidemic of obesity. Investigational antiobesity agents consist of 1) central nervous system agents that affect neurotransmitters or neural ion channels, including antidepressants (bupropion), selective serotonin 2c receptor agonists, antiseizure agents (topiramate, zonisamide), some dopamine antagonists, and cannabinoid-1 receptor antagonists (rimonabant); 2) leptin/insulin/central nervous system pathway agents, including leptin analogues, leptin transport and/or leptin receptor promoters, ciliary neurotrophic factor (Axokine), neuropeptide Y and agouti-related peptide antagonists, proopiomelanocortin and cocaine and amphetamine regulated transcript promoters, alpha-melanocyte-stimulating hormone analogues, melanocortin-4 receptor agonists, and agents that affect insulin metabolism/activity, which include protein-tyrosine phosphatase-1B inhibitors, peroxisome proliferator activated receptor-gamma receptor antagonists, short-acting bromocriptine (ergoset), somatostatin agonists (octreotide), and adiponectin; 3) gastrointestinal-neural pathway agents, including those that increase cholecystokinin activity, increase glucagon-like peptide-1 activity (extendin 4, liraglutide, dipeptidyl peptidase IV inhibitors), and increase protein YY3-36 activity and those that decrease ghrelin activity, as well as amylin analogues (pramlintide); 4) agents that may increase resting metabolic rate ("selective" beta-3 stimulators/agonist, uncoupling protein homologues, and thyroid receptor agonists); and 5) other more diverse agents, including melanin concentrating hormone antagonists, phytostanol analogues, functional oils, P57, amylase inhibitors, growth hormone fragments, synthetic analogues of dehydroepiandrosterone sulfate, antagonists of adipocyte 11B-hydroxysteroid dehydrogenase type 1 activity, corticotropin-releasing hormone agonists, inhibitors of fatty acid synthesis, carboxypeptidase inhibitors, indanones/indanols, aminosterols, and other gastrointestinal lipase inhibitors (ATL962). Finally, an emerging concept is that the development of antiobesity agents must not only reduce fat mass (adiposity) but must also correct fat dysfunction (adiposopathy).
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PMID:Current and investigational antiobesity agents and obesity therapeutic treatment targets. 1534 Jan


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