Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ghrelin is a novel gut-brain peptide that has somatotropic, orexigenic, and adipogenic effects. We examined the preproghrelin Leu72Met polymorphism in 222 obese Korean children to determine whether it is associated with obesity. The frequencies of the Leu72Met polymorphism were 29.3% in obese, 32.3% in overweight, and 32.5% in lean Korean children. No significant difference was found between Met72 carrier and non-carrier obese children with respect to BMI, total body fat, serum triglycerides, total cholesterol, or LDL-cholesterol levels. Our data suggest that the preproghrelin Leu72Met polymorphism is not associated with obesity in children.
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PMID:Preproghrelin Leu72Met polymorphism in obese Korean children. 1645 54

Ghrelin is a novel gut-brain peptide, which exerts somatotropic, orexigenic, and adipogenic effects. Genetic variants of ghrelin have been associated with both obesity and insulin metabolism. In this study, we determined a role of preproghrelin Leu72Met polymorphism on type 2 diabetes mellitus and its relationship to variables studied. Genotypes were assessed by polymerase chain reaction. Frequencies of the Leu72Met polymorphism were found to be 35.4% in the type 2 diabetic patients and 32.5% in the normal controls. The Leu72Met polymorphism was not associated with hypertension, macroangiopathy, retinopathy, serum cholesterol, triglyceride, blood urea nitrogen, HbA(1c), lipoprotein (a), fasting insulin, or 24-hour urinary protein levels in the type 2 diabetic group. However, the Leu72Met polymorphism was clearly associated with serum creatinine levels in the diabetic group, as the Met72 carriers exhibited lower serum creatinine levels than the Met72 noncarriers. Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. However, the Leu72Met polymorphism is associated with serum creatinine levels. These data suggest that Met72 carrier status may be a predictable marker for diabetic nephropathy or renal impairment in type 2 diabetes mellitus.
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PMID:Preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. 1648 81

Ghrelin, the new recently discovered hormone, is a 28 amino-acid acylated peptide predominantly produced by the stomach characterized by a strong GH-releasing activity mediated by the hypothalamic-pituitary GH secretagogues (GHSs) receptors. Ghrelin and GHSs, acting on central and peripheral receptors, exert other actions such as stimulation of ACTH and prolactin secretion, influence on insulin secretion and glucose metabolism, orexigenic effect and modulatory activity on the neuroendocrine and metabolic response to starvation, influence on exocrine gastro-entero-pancreatic functions, cardiovascular activities and modulation of cell proliferation and apoptosis. The wide spectrum of ghrelin action requires further studies to provide critical information on the role of ghrelin and the potential perspectives of its analogues in the clinical practice. This point is of particular interest in the field of pediatric endocrinology and metabolism because the ghrelin story started focusing on GH deficiency and is now extending to aspects that once again are of major relevance such as obesity and eating disorders, regulation of the hypothalamus-pituitary-adrenal and gonadal axis. More studies are needed to evaluate the real impact of ghrelin in different non endocrine processes and the possible use of ghrelin analogues in different diseases condition.
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PMID:Role of ghrelin in the regulation of appetite in children. 1654 Oct 4

Obesity is currently considered one of the most important diseases worldwide due to its high morbidity and mortality rates. The mechanisms involved in the control of satiation, body weight and energy expenditure has led to the discovery of new hormones that participate in the gastrichypothalamic axis in charge of regulating satiation and other obesity-related processes. Ghrelin a novel hormone secreted mainly by gastric tissue, has shed some light on this mechanism. It is a hormone that regulates satiation and body weight by centrally mediated mechanisms, involving neuropeptide Y and Agouti associated proteins. The present review focuses on some important physiological aspects of this hormone.
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PMID:[Ghrelin and the gastro-hypothalamic axis]. 1654 93

According to the World Health Organization, 300 million people are clinically obese worldwide. As a major risk factor in the development of life-threatening diseases such as diabetes, cardiovascular disease and certain cancers, obesity is quickly evolving into a serious public health threat on a global scale. This alarming situation calls for the development of effective treatments, including pharmacological intervention. Many biotechnology and pharmaceutical companies have embarked on the endeavor to develop safe new therapeutics for weight loss and durable weight management. Much progress has been made to improve our understanding of the regulation of energy homeostasis, but this knowledge has not yet translated into new medicines. However, it has led to the identification of molecules that promise to be highly interesting targets for therapeutic intervention. One such molecule is the enteric hormone ghrelin. Ghrelin was identified in 1999 as the endogenous ligand for the growth hormone secretagogue-receptor 1a (GHS-R1a). Soon after its discovery ghrelin was shown to increase food intake, downregulate energy expenditure and conserve body fat, causing weight gain and adipogenesis. Unsurprisingly, these findings placed ghrelin and its receptor on the radar screens of many medical researchers in academia and the pharmaceutical industry. The resulting attention has led to a steadily growing body of evidence in support of ghrelin antagonism as a potential means to ameliorate obesity. But the causes for obesity are manifold, and skepticism about the utility of this approach remains. The current review summarizes the arguments for and against ghrelin as a potential antiobesity target and discusses recent pharmaceutical developments to interfere with this exciting pathway.
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PMID:The promise of ghrelin antagonism in obesity treatment. 1655 Feb 52

Ghrelin, identified as an endogenous ligand for the growth hormone secretagogue receptor, functions as a somatotrophic and orexigenic signal from the stomach. Ghrelin has a unique post-translational modification: the hydroxyl group of the third amino acid, usually a serine but in some species a threonine, is esterified by octanoic acid and is essential for ghrelin's biological activities. The secretion of ghrelin increases under conditions of negative energy-balance, such as starvation, cachexia, and anorexia nervosa, whereas its expression decreases under conditions of positive energy-balance such as feeding, hyperglycemia, and obesity. In addition to having a powerful effect on the secretion of growth hormone, ghrelin stimulates food intake and transduces signals to hypothalamic regulatory nuclei that control energy homeostasis. Thus, it is interesting to note that the stomach may play an important role in not only digestion but also pituitary growth hormone release and central feeding regulation. We summarized recent findings on the integration of ghrelin into neuroendocrine networks that regulate food intake, energy balance, gastrointestinal function and growth.
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PMID:Biological, physiological, and pharmacological aspects of ghrelin. 1661 45

Obese subjects have lower basal and an attenuated decrease of postprandial plasma ghrelin following carbohydrate-rich meals, while the response to protein is unknown. Therefore, plasma ghrelin levels were examined after ingestion of satiating amounts of a protein- or carbohydrate-rich meal in relation to food and energy intake and hunger/satiety ratings in 30 obese subjects followed 240 min later by ad lib sandwiches. Food intake and hunger/satiety ratings were identical while energy intake was significantly greater after bread (861 +/- 62.7 vs. 441 +/- 50.4 kcal, p < 0.001). Second meal food and energy intake were not different. Ghrelin decreased after bread, but increased by 50 pg/ml (p < 0.001) after meat. The corresponding increase of insulin was 55 vs. 9 microU/ml (p < 0.001). Glycerol levels decreased significantly less after the protein meal compared to carbohydrates. After protein glycerol was significantly correlated to the rise of ghrelin but not insulin. These data demonstrate that, in obese subjects, protein has no different satiating effect than carbohydrate despite divergent ghrelin levels. Energy intake corresponds to energy density of the respective food items. Ghrelin response to both meals is qualitatively similar but quantitatively attenuated compared to normal weight subjects. The relationship between ghrelin and glycerol would support recent observations of a possible role of ghrelin in fat metabolism.
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PMID:Ghrelin response to protein and carbohydrate meals in relation to food intake and glycerol levels in obese subjects. 1664 32

Ghrelin is upregulated under negative energy balance conditions, including starvation and hypoglycemia, while it is downregulated under situations of positive energy balance, such as feeding, hyperglycemia and obesity. The aims of this study were to assess potential ghrelin interactions with glucose levels in appetite control and to identify potential mechanisms involving orexigenic and anorexigenic ghrelin mediated signals by using a specific anti-ghrelin antibody. Our results confirm that peripheral ghrelin is an important signal in meal initiation and food intake stimulation. C-fos positive neurons in the PVN increased after insulin or 2-deoxyglucose administration. Moreover, we also demonstrate that peripheral ghrelin blockade with a specific anti-ghrelin antibody reduces, in part, the orexigenic signal induced by insulin and 2-DG administration. Furthermore, when we blocked peripheral ghrelin, c-fos positive CRF neurons and CART expression increased in the PVN, both under hypoglycemia or cytoglycopenia conditions, suggesting a neuronal activation (anorexigenic signalling) in this hypothalamic region. In summary, our findings imply that peripheral ghrelin plays an important role in regulatory "glucostatic" feeding mechanisms due to its role as a "hunger" signal affecting the PVN area, which may contribute to energy homeostasis through both orexigenic/anorexigenic pathways.
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PMID:Peripheral ghrelin participates in glucostatic feeding mechanisms and in the anorexigenic signalling mediated by CART and CRF neurons. 1666 99

Ghrelin has been implicated in the control of food intake and in the long-term regulation of body weight. We theorize that preventing the ability of ghrelin to interact with its receptors, would eventually lead to decreased appetite and thereby decrease body weight gain. To test our hypothesis, pigs were actively immunized against ghrelin. Ghrelin((1-10)) was conjugated to BSA and emulsified in Freund's incomplete adjuvant and diethylaminoethyl-dextran. Primary immunization was given at 19 weeks of age (WOA), with booster immunizations given 20 and 40 days after primary immunization. Body weight (BW) and plasma samples were collected weekly beginning at 19 WOA, and feed intake was measured daily. Fourteen days after primary immunization, the percentage of bound (125)I-ghrelin in plasma from immunized pigs was increased compared with control animals (P<0.001). Voluntary feed intake was decreased more than 15% in animals that were actively immunized against ghrelin compared with controls. By the end of the experiment, immunized pigs weighed 10% less than control animals (P<0.1). Concentrations of GH were increased (P<0.05) in immunized pigs. Apoptosis was not observed in post-mortem samples obtained from the fundic region of the stomach. Our observations suggest that immunization against ghrelin induces mild anorexia. This procedure could potentially be used as a treatment to control caloric intake and obesity.
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PMID:Active immunization against ghrelin decreases weight gain and alters plasma concentrations of growth hormone in growing pigs. 1679 35

Ghrelin, an acylated upper gastrointestinal peptide, is the only known orexigenic hormone. Considerable evidence implicates ghrelin in mealtime hunger and meal initiation. Circulating levels decrease with feeding and increase before meals, achieving concentrations sufficient to stimulate hunger and food intake. Preprandial ghrelin surges occur before every meal on various fixed feeding schedules and also among individuals initiating meals voluntarily without time- or food-related cues. Ghrelin injections stimulate food intake rapidly and transiently, primarily by increasing appetitive feeding behaviors and the number of meals. Preprandial ghrelin surges are probably triggered by sympathetic nervous output. Postprandial suppression is not mediated by nutrients in the stomach or duodenum, where most ghrelin is produced. Rather, it results from post-ingestive increases in lower intestinal osmolarity (information probably relayed to the foregut via enteric nervous signaling), as well as from insulin surges. Consequently, ingested lipids suppress ghrelin poorly compared with other macronutrients. Beyond a probable role in meal initiation, ghrelin also fulfills established criteria for an adiposity-related hormone involved in long-term body-weight regulation. Ghrelin levels circulate in relation to energy stores and manifest compensatory changes in response to body-weight alterations. Ghrelin crosses the blood-brain barrier and stimulates food intake by acting on several classical body-weight regulatory centers, including the hypothalamus, hindbrain, and mesolimbic reward system. Chronic ghrelin administration increases body weight via diverse, concerted actions on food intake, energy expenditure, and fuel utilization. Congenital ablation of the ghrelin or ghrelin-receptor gene causes resistance to diet-induced obesity, and pharmacologic ghrelin blockade reduces food intake and body weight. Ghrelin levels are high in Prader-Willi syndrome and low after gastric bypass surgery, possibly contributing to body-weight alterations in these settings. Extant evidence favors roles for ghrelin in both short-term meal initiation and long-term energy homeostasis, making it an attractive target for drugs to treat obesity and/or wasting disorders.
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PMID:Ghrelin and the short- and long-term regulation of appetite and body weight. 1685 20


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