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

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

The C57BL/6J mice are inbred strains and develop the metabolic syndrome of obesity, hyperinsulinemia, hyperglycemia, and hypertension, when fed a high-fat diet. These features are similar to those observed in the human metabolic syndrome. This article examined the effect of fat-enriched (FE) diet on the pattern of distribution of insulin-, glucagon-, somatostatin-, and pancreatic polypeptide (PP)-positive cells in the pancreatic islets of C57BL/6J mice using immunohistochemical methods. Insulin-immunoreactive cells were observed in both the peripheral and central regions of the islets of Langerhans in both FE- and control diet-fed mice. The percentage distribution of insulin-positive cells was similar in FE (83.5 +/- 6.4) compared to control diet-fed C57BL/6J mice (83.8 +/- 6.5). Glucagon-containing cells were discerned in the periphery of pancreatic islets in both FE- and control diet-fed mice. The percentage distribution of glucagon was not statistically different in mice fed with FE (9.9 +/- 2.7) compared to control diet (11.3 +/- 4.9). Somatostatin-positive cells were seen in the outer part of the islet of Langerhans and constitute 12.1% (+/-6.3) and 10% (+/-5.5) of pancreatic islet cells in FE- and control diet-fed mice, respectively. PP-immunoreactive cells were observed in the peripheral region of the pancreatic islets of both FE- and control diet-fed mice. The percentage distribution of PP-positive cells was significantly (2.0 +/- 1.2) lower compared to control (5.1 +/- 2.4). In conclusion, the number of PP is significantly reduced in FE diet-fed mice and may play a role in the pathogenesis of diet-induced metabolic syndrome in C57BL/6J mice.
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PMID:The effect of a fat-enriched diet on the pattern of distribution of pancreatic islet cells in the C57BL/6J mice. 1715 15

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

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

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

Peptide YY (PYY), a 36-amino-acid peptide, is secreted primarily from L-cells residing in the intestinal mucosa of the ileum and large intestine. PYY, which belongs to a family of peptides including neuropeptide Y (NPY) and pancreatic polypeptide, is released into the circulation as PYY(1-36) and PYY(3-36); the latter is the major form of PYY in gut mucosal endocrine cells and throughout the circulation. Plasma PYY levels begin to rise within 15 min after starting to eat and plateau within approximately 90 min, remaining elevated for up to 6 h. Exogenous administration of PYY(3-36) reduces energy intake and body weight in both humans and animals. Via Y2 receptors, the satiety signal mediated by PYY inhibits NPY neurons and activates pro-opiomelanocortin neurons within the hypothalamic arcuate nucleus. Peripheral PYY(3-36) binds Y2 receptors on vagal afferent terminals to transmit the satiety signal to the brain. PYY(3-36) may have therapeutic potential in human obesity.
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PMID:The role of PYY in feeding regulation. 1792 Jul 5

The increasing prevalence of obesity worldwide has imparted renewed impetus to the study of the mechanisms of appetite regulation. Digestion and nutrient absorption take place in the gastrointestinal (GI) tract, whereas food intake is controlled by neuronal circuits in the central nervous system. The need for gut-brain cross talk is therefore clear. It is now recognized that hormones released into the circulation from the GI tract in response to nutritional stimuli form a key component of this gut-brain axis. Peptides such as glucagon-like peptide-1, oxyntomodulin, pancreatic polypeptide, and peptide YY3-36 reduce food intake in both animal models and in humans. Physiologically, such peptides are thought to act as satiety signals and meal terminators. Here, we review the current state of the field of the effects of gut hormone action on appetite control.
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PMID:Gastrointestinal satiety signals. 1793

Food intake and bodyweight are tightly regulated by the brainstem, hypothalamus and reward circuits. These centres integrate diverse cognitive inputs with humoral and neuronal signals of nutritional status. Our knowledge of the role of gut hormones in this complex homeostatic system has expanded enormously in recent years. This review discusses both the role of gut hormones in appetite regulation, and the current state of development of gut hormone-based obesity therapies, with a particular focus on pancreatic polypeptide, peptide YY, amylin, glucagon-like peptide-1, oxyntomodulin, cholecystokinin and ghrelin. Several gut hormone-based treatments for obesity are under investigation in phase II and III clinical trials, and many more are in the pipeline.
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PMID:Gut hormones as potential new targets for appetite regulation and the treatment of obesity. 1819 23

The current obesity epidemic is fuelled by the availability of highly palatable, calorie-dense food, and the low requirement for physical activity in our modern environment. If energy intake exceeds energy use, the excess calories are stored as body fat. Although the body has mechanisms that act to maintain body weight over time, they primarily defend against starvation and are less robust in preventing the development of obesity. Knowledge of this homeostatic system that controls body weight has increased exponentially over the last decade and has revealed new possibilities for the treatment of obesity and its associated comorbidities. One therapeutic target is the development of agents based on the gastrointestinal hormones that control appetite. This review discusses the hormones oxyntomodulin, peptide YY, glucagon-like peptide 1, pancreatic polypeptide, and ghrelin and their emerging potential as anti-obesity treatments.
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PMID:Can gut hormones control appetite and prevent obesity? 1822 98


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