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

The neuropeptide Y (NPY) family of peptides and receptors regulate food intake. Inherited variation in this pathway could influence susceptibility to obesity and its complications, including type 2 diabetes. We genotyped a set of 71 single nucleotide polymorphisms (SNPs) that capture the most common variation in NPY, PPY, PYY, NPY1R, NPY2R, and NPY5R in 2,800 individuals of recent European ancestry drawn from the near extremes of BMI distribution. Five SNPs located upstream of NPY2R were nominally associated with BMI in men (P values = 0.001-0.009, odds ratios [ORs] 1.27-1.34). No association with BMI was observed in women, and no consistent associations were observed for other genes in this pathway. We attempted to replicate the association with BMI in 2,500 men and tested these SNPs for association with type 2 diabetes in 8,000 samples. We observed association with BMI in men in only one replication sample and saw no association in the combined replication samples (P = 0.154, OR = 1.09). Finally, a 9% haplotype was associated with type 2 diabetes in men (P = 1.73 x 10(-4), OR = 1.36) and not in women. Variation in this pathway likely does not have a major influence on BMI, although small effects cannot be ruled out; NPY2R should be considered a candidate gene for type 2 diabetes in men.
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PMID:Association studies of BMI and type 2 diabetes in the neuropeptide Y pathway: a possible role for NPY2R as a candidate gene for type 2 diabetes in men. 1732 59

Selective activation of the NPY2 receptor to suppress appetite provides an approach to obesity management. Selective NPY2 PEGylated peptide agonists are described that consist of a peptide core corresponding to residues 25-36 of PYY and a nonpeptidic moiety at the peptide N-terminus that contributes to in vitro potency and in vivo efficacy and provides a PEGylation site. The lead peptide elicits a dose-dependent reduction of food intake in lean mice and of food intake, body weight, and fat mass in DIO mice.
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PMID:Novel selective neuropeptide Y2 receptor PEGylated peptide agonists reduce food intake and body weight in mice. 1742 99

Metabolic syndrome (MS), defined as central obesity, hyperinsulinemia, insulin resistance, hypertension, dyslipidemia and glucose intolerance, has been associated with inflammatory biomarkers and cardiovascular diseases. This study was carried out on three groups of women; lean controls, moderately obese with MS (OB-MS) and morbidly obese with MS (MOB-MS). The main objectives were: 1. to analyze the plasma levels of total and acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), gastrin and insulin levels under basal conditions and in response to a standard mixed meal, and 2. to elucidate the relationship between the plasma levels of these gut peptides and metabolic syndrome parameters. Plasma levels of the gut hormones were measured by radioimmunoassays at time 0 just before the meal and at 30, 60 and 120 min after a meal ingestion. Traditional lipid profile and high-sensitivity C reactive protein (hs-CRP), the strongest biomarker of inflammation were also determined in OB-MS and MOB-MS. When compared to OB-MS, MOB-MS exhibited much higher anthropometric parameters such as waist circumference, higher fat mass and higher plasma levels of low density lipoprotein-cholesterol (LDL-C) and hs-CRP. Both these obese groups revealed significantly higher values of body mass index (BMI), fat mass, total cholesterol (TC), LDL-C, fasting glucose, fasting insulin, insulin resistance (IR) calculated from homeostatic model assessment (HOMA) and hs-CRP compared to the values recorded in lean subjects. Fasting PYY(3-36) level was lower, while fasting acylated ghrelin was higher in MOB-MS than in OB-MS. Plasma total and acylated ghrelin levels were significantly lower in OB-MS compared to lean women. In MOB-MS women the fasting PYY(3-36) levels were lower compared to lean controls and OB-MS, whilst postprandially in both OB-MS and MOB-MS, it was much lower than in lean women. The fasting plasma levels of total and acylated ghrelin and their postprandial decrease were significantly smaller in both obese groups compared to lean subjects. Plasma hs-CRP levels correlated positively with BMI, waist circumference, fat mass, fasting glucose, HOMA IR and fasting active ghrelin, whilst it negatively correlated with plasma fasting and total ghrelin. Moreover, plasma fasting acylated ghrelin correlated positively with fat mass. Fasting total ghrelin correlated positively with BMI, HDL-C and negatively with HOMA IR. We conclude that MS features of obesity are closely related to fasting and postprandial alterations of concentrations of PYY(3-36), CCK and ghrelin, suggesting that determination of gut hormones controlling food intake might be considered as a valuable tool to assess the progression of MS to comorbidities of obesity.
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PMID:Basal and postprandial plasma levels of PYY, ghrelin, cholecystokinin, gastrin and insulin in women with moderate and morbid obesity and metabolic syndrome. 1744 25

Maternal obesity has been reported as a risk factor for various maternal and fetal complications. The aim of the present study was to examine the patterns of basal and postprandial plasma concentrations of certain gut hormones affecting food intake such as acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), insulin and glucose in pregnant women with varying body mass gain during physiological pregnancy. The study included 34 women with singleton pregnancies in the 2(nd) trimester of gestation. The examined pregnant women were divided into 4 groups; I. control pregnancy (CP) with weight gain below 0.5 kg/week; II. overweight low weight gain <1 kg/week (OLWG), III. overweight high weight gain >1 kg/week (OHWG); morbidly obese pregnant with weight gain >1.5 kg/week (MOP). The basal acylated-ghrelin levels in MOP subjects were significantly higher than those in CP and no usual suppression of acylated ghrelin after the meal observed in CP as well as in OLWG and OHWG was found in MOP women. Basal PYY(3-36) plasma levels were similar in CP, OLWG and OHWG but in MOP was significantly reduced and no significant increase in hormone level, typically observed in CP, was detected after a meal in overweight or obese women studied. The fasting CCK and C-reactive protein (CRP) levels in MOP subjects were significantly higher than those in CP and other overweight women. In conclusion, we found that pregnant women with overweight and obesity exhibit significant changes in fasting and postprandial gut hormones affecting food intake such as acylated ghrelin, PYY(3-36) and CCK as well as in CRP and these changes might contribute, at least in part, the development of obesity in pregnancy.
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PMID:Basal and postprandial gut peptides affecting food intake in lean and obese pregnant women. 1744 26

Many peptides are synthesized and released from the gastrointestinal tract. Although their roles in the regulation of gastrointestinal function have been known for some time, it is now evident that they also physiologically influence eating behavior. Our understanding of how neurohormonal gut-brain signaling regulates energy homeostasis has advanced significantly in recent years. Ghrelin is an orexigenic peptide produced by the stomach, which appears to act as a meal initiator. Satiety signals derived from the intestine and pancreas include peptide YY, pancreatic polypeptide, glucagon-like peptide 1, oxyntomodulin, and cholecystokinin. Recent research suggests that gut hormones can be manipulated to regulate energy balance in humans, and that obese subjects retain sensitivity to the actions of gut hormones. Gut hormone-based therapies may thus provide an effective and well-tolerated treatment for obesity.
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PMID:Gut hormones and appetite control. 1749 7

Obesity is a major public health problem associated with morbidity and mortality and continues to increase worldwide. This review focuses on the regions of the brain that are important in appetite regulation and the circulating factors implicated in the control of food intake. The hypothalamus is critical in the regulation of food intake containing neural circuits, which produce a number of peptides that influence food intake. The arcuate nucleus of the hypothalamus produces both orexigenic peptides (agouti-related protein and neuropeptide Y) and anorectic peptides (alpha-melanocyte-stimulating hormone and cocaine- and amphetamine-related transcript). The lateral hypothalamus produces the orexigenic peptides (melanin-concentrating hormone and orexins). Other hypothalamic factors recently implicated in appetite regulation include the endocannabinoids, brain-derived neurotrophic factor, nesfatin-1, AMP-activated protein kinase, mammalian target of rapamycin protein, and protein tyrosine phosphatase. Circulating factors that affect food intake mediate their effects by signaling to the hypothalamus and/or brainstem. A number of circulating factors are produced by peripheral organs, for example, leptin by adipose tissue, insulin and pancreatic polypeptide by the pancreas, gut hormones (e.g., ghrelin, obestatin, glucagon-like peptide-1, oxyntomodulin, peptide YY), and triiodothyronine by the thyroid gland. Circulating carbohydrates, lipids, and amino acids also affect appetite regulation. Knowledge regarding appetite regulation has vastly expanded in recent years providing targets for antiobesity drug design.
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PMID:Appetite regulation: an overview. 1754 73

Prader-Willi syndrome (PWS) is a contiguous gene syndrome characterized by uncontrollable eating or hyperphagia. Several studies have confirmed that plasma ghrelin levels are markedly elevated in PWS adults and children. The study of anorexigenic hormones is of interest because of their regulation of appetite by negative signals. To study the pattern and response of the anorexigenic hormones such as cholecystokinin (CCK) and peptide YY (PYY) to a meal in PWS, we measured the plasma CCK, PYY, ghrelin and serum insulin levels in PWS patients (n=4) and in controls (n=4) hourly for a day, and analyzed hormone levels and hormonal responses to meals. Repeated measures of ANOVA of hormone levels demonstrated that only insulin levels decreased (p=0.013) and CCK (p=0.005) and ghrelin (p=0.0007) increased in PWS over 24 hr. However, no significant group x time interactions (ghrelin: p=0.89, CCK: p=0.93, PYY: p=0.68 and insulin: p=0.85) were observed; in addition, there were no differences in an assessment of a three-hour area under the curve after breakfast. These results suggest that the response pattern of hormones to meals in PWS patients parallels that of normal controls. In addition, the decrease of insulin levels over 24 hr, in spite of obesity and elevated ghrelin levels, suggests that the baseline insulin level, not the insulin response to meals, may be abnormal in patients with PWS.
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PMID:Peptide YY, cholecystokinin, insulin and ghrelin response to meal did not change, but mean serum levels of insulin is reduced in children with Prader-Willi syndrome. 1759 50

It is well known that the peripheral peptide YY (PYY)-central neuropeptide Y (NPY) Y2 receptor axis plays an important role in promoting negative energy balance regulation. Both the hypothalamus and medulla oblongata express a high level of Y2 receptors; however, the functional role of this receptor in chronic high-fat diet-induced obesity has not been fully examined. Using quantitative autoradiography, this study measured binding densities of total [(125)I]PYY and Y2 receptors in the hypothalamus and medulla of chronic high-fat diet-induced obese (DIO), obese-resistant, and low-fat-fed mice. Plasma PYY was also measured using RIA after 22 wk of dietary intervention. The results revealed that body weight gain was significantly higher in the obese mice, compared with the lean mice. Furthermore, PYY and NPY Y2 receptor binding densities in the medulla of the obese mice were significantly higher, compared with the lean mice, whereas the level of plasma PYY was significantly lower in the DIO mice than the low-fat-fed mice. In conclusion, this study showed that the DIO mice had low plasma PYY, which may have caused a compensatory up-regulation of PYY and Y2 receptor densities in the medulla. A low-level response of PYY-medullary regulation to positive energy balance may have contributed to the development of high-fat diet-induced obesity in DIO mice; conversely, a normal response of this regulatory axis in the obese-resistant mice may have contributed to the maintenance of body weight while on a high-fat diet.
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PMID:Decreased plasma peptide YY accompanied by elevated peptide YY and Y2 receptor binding densities in the medulla oblongata of diet-induced obese mice. 1761 45

Roux-en-Y gastric bypass (RYGB) is the most effective therapy for morbid obesity, but it has a approximately 20% failure rate. To test our hypothesis that outcome depends on differential modifications of several energy-related systems, we used our established RYGB model in Sprague-Dawley diet-induced obese (DIO) rats to determine mechanisms contributing to successful (RGYB-S) or failed (RYGB-F) RYGB. DIO rats were randomized to RYGB, sham-operated Obese, and sham-operated obese pair-fed linked to RYGB (PF) groups. Body weight (BW), caloric intake (CI), and fecal output (FO) were recorded daily for 90 days, food efficiency (FE) was calculated, and morphological changes were determined. d-Xylose and fat absorption were studied. Glucose-stimulated vagal efferent nerve firing rates of stomach were recorded. Gut, adipose, and thyroid hormones were measured in plasma. Mitochondrial respiratory complexes in skeletal muscle and expression of energy-related hypothalamic and fat peptides, receptors, and enzymes were quantified. A 25% failure rate occurred. RYGB-S, RYGB-F, and PF rats showed rapid BW decrease vs. Obese rats, followed by sustained BW loss in RYGB-S rats. RYGB-F and PF rats gradually increased BW. BW loss in RYGB-S rats is achieved not only by RYGB-induced decreased CI and increased FO, but also via sympathetic nervous system activation, driven by increased peptide YY, CRF, and orexin signaling, decreasing FE and energy storage, demonstrated by reduced fat mass associated with the upregulation of mitochondrial uncoupling protein-2 in fat. These events override the compensatory response to the drop in leptin levels aimed at conserving energy.
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PMID:Characterization of weight loss and weight regain mechanisms after Roux-en-Y gastric bypass in rats. 1762 26

Selective activation of the neuropeptide Y (NPY)2 receptor to suppress appetite provides a promising approach to obesity management. A selective NPY2 polyethylene glycol-conjugated (PEGylated) peptide agonist is described that consists of a peptide core corresponding to residues 13 to 36 of human peptide YY (PYY) and a nonpeptidic moiety (2-mercaptonicotinic acid) at the peptide N terminus that is derivatized with 20-kDa monomethoxypolyethylene glycol. The PEGylated peptide elicits a dose-dependent reduction in food intake in lean C57BL/6 mice and Wistar rats that persists for 72 and 48 h, respectively. The effect on food intake in lean C57BL/6 mice is blocked by the selective NPY2 antagonist BIIE0246 (N-[(1S)-4-[(aminoiminomethyl)amino]-1-[[[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]amino]carbonyl]butyl]-1-[2-[4-(6,11-dihydro-6-oxo-5H-dibenz[b,e]azepin-11-yl)-1-piperazinyl]-2-oxoethyl]-cyclopentaneacetamide formate). A dose-dependent reduction in body weight in diet-induced obese (DIO) mice is seen following daily dosing for 14 days. The reduction in body weight is sustained following dosing for 40 days, and it is accompanied by an increase in plasma adiponectin. Improvements in glucose disposal and in plasma insulin and glucose levels that are risk factors for type II diabetes are observed following once-daily subcutaneous dosing in DIO mice. The results provide evidence from two animal species that the long-acting selective NPY2 peptide agonist has potential for obesity management.
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PMID:A novel long-acting selective neuropeptide Y2 receptor polyethylene glycol-conjugated peptide agonist reduces food intake and body weight and improves glucose metabolism in rodents. 1767 Oct 99


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