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

Obesity represents the most prevalent nutritional problem worldwide which in the long run predisposes to development of diabetes mellitus, hypertension, endometrial carcinoma, osteoarthritis, gall stones and cardiovascular diseases. Despite significant reductions in dietary fat consumption, the prevalence of obesity is on a rise and is taking on pandemic proportions. Obesity develops when energy intake exceeds energy expenditure over time. Recently, a close evolutionary relationship between the peripheral and hypothalamic neuropeptides has become apparent. The hypothalamus being the central feeding organ mediates regulation of short-term and long-term dietary intake via synthesis of various orexigenic and anorectic neuropeptides. The structure and function of many hypothalamic peptides (neuropeptide Y (NPY), melanocortins, agouti-related peptide (AGRP), cocaine and amphetamine regulated transcript (CART), melanin concentrating hormone (MCH), orexins have been characterized in rodent models The peripheral neuropeptides such as cholecystokinin (CCK), ghrelin, peptide YY (PYY3-36), amylin, bombesin regulate important gastrointestinal functions such as motility, secretion, absorption, provide feedback to the central nervous system on availability of nutrients and may play a part in regulating food intake. The pharmacological potential of several endogenous peripheral peptides released prior to, during and/or after feeding are being explored. Long-term regulation is provided by the main circulating hormones leptin and insulin. These systems implicated in hypothalamic appetite regulation provide potential targets for treatment of obesity which could potentially pass into clinical development in the next 5 years. This review summarizes various effects and interrelationship of these central and peripheral neuropeptides in metabolism, obesity and their potential role as targets for treatment of obesity.
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PMID:Role of neuropeptides in appetite regulation and obesity--a review. 1693 29

The gastrointestinal tract, besides digesting and processing nutrients, is now regarded as an endocrine organ able to modulate appetite, satiety, and carbohydrate metabolism. Several enteroendocrine cells produce numerous peptides codifying either orexigenic (ghrelin, orexins) or anorexigenic signals (pancreatic polypeptide, peptide YY, cholecystokinin, amylin, bombesin homologs, apolipoprotein A-IV, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, oxyntomodulin), which interact in a complex network with other peripheral signals of energy balance and with different neuropeptides involved in the central control of appetite and energy homeostasis. The growing knowledge of the actions of these gastrointestinal peptides on appetite regulation and carbohydrate metabolism, and subsequent synthesis of analogs, particularly those derived from amylin and incretins, herald a new era in the therapy of 2 closely related diseases, obesity and type 2 diabetes mellitus.
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PMID:[New approaches in obesity treatment: the gastrointestinal tract as an endocrine organ]. 1694 16

Dietary protein enhances satiety and promotes weight loss, but the mechanisms by which appetite is affected remain unclear. We investigated the role of gut hormones, key regulators of ingestive behavior, in mediating the satiating effects of different macronutrients. In normal-weight and obese human subjects, high-protein intake induced the greatest release of the anorectic hormone peptide YY (PYY) and the most pronounced satiety. Long-term augmentation of dietary protein in mice increased plasma PYY levels, decreased food intake, and reduced adiposity. To directly determine the role of PYY in mediating the satiating effects of protein, we generated Pyy null mice, which were selectively resistant to the satiating and weight-reducing effects of protein and developed marked obesity that was reversed by exogenous PYY treatment. Our findings suggest that modulating the release of endogenous satiety factors, such as PYY, through alteration of specific diet constituents could provide a rational therapy for obesity.
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PMID:Critical role for peptide YY in protein-mediated satiation and body-weight regulation. 1695 Jan 39

Low circulating peptide YY (PYY) levels are reported in obese and type II diabetic subjects and results from PYY knockout animals suggests that PYY deficiency may have a causative role in the etiology of obesity and type 2 diabetes. Here, our aims were to determine whether people with a genetic predisposition to developing type 2 diabetes and obesity differ from otherwise similar subjects without such family history, in fasting or meal-related PYY levels, fasting insulin, insulin secretion (HOMA-B) and insulin sensitivity. We also investigated whether PYY ablation affects the intrinsic ability of islets to secrete insulin, which may be a contributing factor to the hyperinsulinemia observed in PYY knockout mice. Healthy female first-degree relatives of people with type 2 diabetes were matched for age, gender and BMI to control subjects but had significantly lower insulin sensitivity (p<0.05). Relatives also had significantly lower fasting serum PYY levels than controls (p<0.05), but their PYY response to a high fat meal (4250 kJ, 73% fat) was not significantly different. Fasting PYY level correlated positively with glucose infusion rate (r=0.713, p=0.002) and fasting adiponectin (r=0.5, p=0.02). Islets of Langerhans from PYY knockout mice were found to hypersecrete insulin in response to 25 mM glucose (p<0.05). These data demonstrate that lack of PYY enhances insulin secretion from the Islets of Langerhans and that low fasting PYY levels are associated with insulin resistance in humans. Together, these findings suggest that low circulating levels of PYY could contribute to hyperinsulinemia and insulin resistance, and possibly contribute to subsequent development of obesity and type 2 diabetes.
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PMID:Low serum PYY is linked to insulin resistance in first-degree relatives of subjects with type 2 diabetes. 1704 46

Obesity and type II diabetes mellitus have reached epidemic proportions. From this perspective, knowledge about the regulation of satiety and food intake is more important than ever. The gut releases several peptides upon feeding, which affect hypothalamic pathways involved in the regulation of satiety and metabolism. Within the hypothalamus, there are complex interactions between many nuclei of which the arcuate nucleus is considered as one of the most important hypothalamic centres that regulates food intake. The neuropeptides, which are present in the hypothalamus and are involved in regulating food intake, also play a key role in regulating glucose metabolism and energy expenditure. In synchrony with the effects of those neuropeptides, gastrointestinal hormones also affect glucose metabolism and energy expenditure. In this review, the effects of the gastrointestinal hormones ghrelin, cholecystokinin, peptide YY, glucagon-like peptide, oxyntomodulin and gastric inhibitory polypeptide on glucose and energy metabolism are reviewed. These gut hormones affect glucose metabolism at different levels: by altering food intake and body weight, and thereby insulin sensitivity; by affecting gastric delay and gut motility, and thereby meal-related fluctuations in glucose levels; by affecting insulin secretion, and thereby plasma glucose levels, and by affecting tissue specific insulin sensitivity of glucose metabolism. These observations point to the notion of a major role of the gut-brain axis in the integrative physiology of whole body fuel metabolism.
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PMID:Gut-brain axis: regulation of glucose metabolism. 1707 64

Gut hormones signal to the central nervous system to influence energy homeostasis. Evidence supports the existence of a system in the gut that senses the presence of food in the gastrointestinal tract and signals to the brain via neural and endocrine mechanisms to regulate short-term appetite and satiety. Recent evidence has shown that specific gut hormones administered at physiological or pathophysiological concentrations can influence appetite in rodents and humans. Gut hormones therefore have an important physiological role in postprandial satiety, and gut hormone signaling systems represent important pharmaceutical targets for potential antiobesity therapies. Our laboratory investigates the role of gut hormones in energy homeostasis and has a particular interest in this field of translational research. In this review we describe our initial studies and the results of more recent investigations into the effects of the gastric hormone ghrelin and the intestinal hormones peptide YY, pancreatic polypeptide, glucagon-like peptide-1, and oxyntomodulin on energy homeostasis. We also speculate on the role of gut hormones in the future treatment of obesity.
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PMID:Gut peptides in the regulation of food intake and energy homeostasis. 1707 90

Excessive weight gain is directly related to a positive energy balance which is due to both a decreased physical activity and overeating. Obesity prevalence is increasing since thirty years and the treatment of obesities is particularly necessary to solve this public health and economical problem. The receptors of numerous hypothalamic neuropeptides are potential targets for such drug treatments. Hormones of the gastro-intestinal tract or produced by the adipose tissue directly interact with these central pathways to regulate feeding behavior. The use of leptin, an adipose tissue hormone that inhibits food intake, has not been conclusive because of the development of leptin resistance in obese subjects. Similar disappointing results have been obtained with antagonists of neuropeptide Y (NPY), one of the most potent orexigenic peptide. This was linked to the complexity and redundancy of the circuits involved in feeding regulation. Consequently, a multitherapy targeting several pathways simultaneously is probably the best option to cure obesity. Among these pathways, PYY 3-36 has been tested in man and some encouraging data have been obtained in animals with antagonists of some other orexigenic peptides such as orexins and melanin-concentrating hormone. A few gene therapy trials in the rat brain have restored interest for the leptin and NPY pathways. Their general use is however not planed in a next future. According to the type of obesity, these new treatments might be associated with either current (or almost current) drugs acting either on serotoninergic/catecholaminergic or cannabinoid pathways, or with surgery. Behavioral changes (food intake, exercise) and preventive actions during early life (in utero, young children) will remain for a while the best solutions to limit overweight development. The new treatments will help obese people to adhere to these behavioral changes by improving their efficiency to induce weight loss.
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PMID:[Feeding regulatory peptides: hopes and limits for the treatment of obesities]. 1714 57

Fasting and postprandial levels of human peptide YY (PYY) were recently found to be lower in obesity. To investigate whether PYY levels are correspondingly high in patients with anorexia nervosa, PYY concentrations were analyzed under basal conditions and in response to a liquid meal. We investigated PYY plasma levels in 16 female anorectic (BMI 15.2+/-0.3 kg/m2) and seven lean subjects (BMI 21.3+/-0.6 kg/m2) before and after ingestion of a liquid meal (250 kcal; 15% protein, 55% carbohydrates, and 30% fat). PYY levels were analyzed using PYY ELISA (DSL, USA). Values are given as mean+/-SEM. Basal PYY levels in anorectic patients (89.0+/-14.4 pg/mL) were not significantly different from lean subjects (64.1+/-12.1 pg/mL). Postprandial PYY levels in healthy volunteers increased significantly after 20 and 60 min (80.4+/-12.7 and 96.0+/-19.9 pg/mL, respectively). In anorectic women PYY was increased at 20 min (137.9+/-19.5 pg/mL) and at 60 min (151.3+/-19.2 pg/mL). No difference was found between both groups. We conclude that basal and postprandial PYY levels in normal weight women are not different from anorectic patients. We could not confirm the recently published blunted postprandial PYY response in anorexia, a finding that merits further study.
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PMID:Peptide YY release in anorectic patients after liquid meal. 1715 59

Obesity is associated with significant health risks including stroke and heart disease. The prevalence of obesity has dramatically increased over the past 20 years. Although the development of obesity is clearly related to changing lifestyles, the central nervous system plays a key role in regulation of energy balance. To develop effective strategies for treating obesity, we must gain a clearer understanding of the neuro-circuitry and signaling mechanisms involved. Toward this end, recent progress has been made in the understanding of the roles played by the sensory circumventricular organs (CVOs) of the brain. These areas lack the normal blood-brain barrier and thus act as transducers of signals between the blood, other centers in the brain, and the cerebrospinal fluid. This review focuses on the roles played by the sensory CVOs in detecting and responding to a number of signals that carry information regarding nutritional status, including cholecystokinin, amylin, ghrelin, peptide YY, pancreatic polypeptide, leptin, adiponectin, and glucose.
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PMID:Making sense of it: roles of the sensory circumventricular organs in feeding and regulation of energy homeostasis. 1720 82

Activation of the NPY2 receptor to reduce appetite while avoiding activation of the NPY1 and NPY5 receptors that stimulate feeding provides a pharmaceutical approach to modulate food intake. The naturally occurring peptide and development candidate PYY(3-36) is a non-selective NPY1, NPY2, and NPY5 agonist of limited in vivo duration of action. N-terminal modification with 20 kDa PEG of a selective NPY2 receptor agonist peptide results in a long-acting agent that outperforms PYY(3-36) in reducing food intake in mice. The results suggest that PEGylated, selective NPY2 peptide agonists offer a significantly improved therapeutic benefit over PYY(3-36) for obesity management.
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PMID:A long-acting selective neuropeptide Y2 receptor PEGylated peptide agonist reduces food intake in mice. 1729 7


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