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

Following the discovery of secretin in 1902, a host of further peptide hormones that are synthesised and released from the gastrointestinal tract have been identified. While their roles in the regulation of gastrointestinal function have been known for some time, it is now evident that many of these hormones also physiologically regulate energy balance. Our understanding of how gut hormones signal to the brain has advanced significantly in recent years. Several hormones, including peptide YY, pancreatic polypeptide, oxyntomodulin, glucagon-like peptide 1 and cholecystokinin function as satiety signals. In contrast, only ghrelin, produced by the stomach, has emerged as a putative hunger signal, appearing to act both as a meal initiator and a long-term body weight regulator. Recent research suggests that gut hormones can be manipulated to regulate energy balance in man and that obese subjects retain sensitivity to the actions of gut hormones. The worldwide obesity pandemic continues unabated, despite public health initiatives and current best therapy. Future gut hormone-based therapies may provide an effective and well-tolerated treatment for obesity.
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PMID:Gut and hormones and obesity. 1823 Sep 2

Obesity is a global epidemic; increased consumption of energy-dense food and reduced physical activity levels are likely to be the main drivers. Previous cross-sectional research has shown that sedentary males, unlike their active counterparts, are unable to compensate for previous energy intake (EI). Using a longitudinal design a 6-week exercise intervention was found to improve short-term appetite control, leading to a more 'sensitive' eating behaviour in response to previous EI, both acutely at a test meal and for the next 24 h. Although the mechanisms whereby acute and chronic exercise improves short-term appetite remain unknown, post-ingestive satiety peptides are likely to be involved. Acute exercise was found to increase postprandial levels of polypeptide YY, glucagon-like peptide-1 and pancreatic polypeptide but to have no impact on ghrelin, suggesting that exercise can trigger physiological changes in satiety hormone secretion that could help in appetite control and weight maintenance. In the context of an increased availability of highly-palatable food, dietary restraint may be increasingly important. Although restraint has been associated with abnormal eating behaviour, in the laboratory no counter-regulation was found in restrained eaters when presented with a buffet meal 60 min after a high-energy preload or when a pasta-meal was presented 3 h after preloading. Although restraint was not found to impact on polypeptide YY or TAG, lower postprandial glucose and insulin plasma levels were observed in restrained eaters, together with increased feelings of fullness. In conclusion, short-term appetite control seems to be favourably modified by exercise, while the impact of restraint on appetite seems to be more complex.
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PMID:Effects of exercise and restrained eating behaviour on appetite control. 1823 29

The prevalence of obesity has reached epidemic proportions worldwide and the incidence of overweight and obesity continues to rise. Diet plays a significant role in the modulation of body weight and there is some evidence to suggest that calcium or dairy intake may modulate body weight and body fat mass. Several mechanisms through which calcium or dairy products may affect body weight or fat have been suggested, including a possible effect on appetite and food intake. A recent study investigated to what extent people could compensate for increased energy intake from dairy products and found that a 7-day increase in dairy intake had no effect on appetite and no evidence of complete compensation for the raised energy intake. In another study, the effects of altered calcium content of a dairy-based test meal was evaluated in obese subjects; the findings indicated that although a higher calcium content of the meal reduced the extent of post-prandial chylomicron-associated triglyceridemia, there was no effect on appetite-related hormones (CCK, ghrelin, GLP-1, or PPY) or on energy intake from a subsequent ad libitum test meal. Thus, this new evidence does not support the hypothesis that high calcium or dairy intake reduces appetite or food intake.
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PMID:Can the controversial relationship between dietary calcium and body weight be mechanistically explained by alterations in appetite and food intake? 1882 56

Orlistat, an inhibitor of digestive lipases, is widely used for the treatment of obesity. Previous reports on the effect of orally ingested orlistat together with a meal on gastric emptying and secretion of gut peptides that modulate postprandial responses are controversial. We investigated the effect of ingested orlistat on gastric emptying and plasma responses of gut peptides in response to a solid mixed meal with a moderate energy load. In healthy subjects, gastric emptying was determined using scintigraphy and studies were performed without and with 120 mg of orlistat in pellet form in random order. Orlistat shortened t lag and t half and decreased the area under the gastric emptying curve. Orlistat significantly attenuated the secretion of glucose-dependent insulinotropic polypeptide (GIP) but did not alter the plasma responses of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and insulin. There was no peptide YY (PYY) response. Area under the curve of gastric emptying was positively correlated with integrated secretion of GIP (r=0.786) in orlistat and was negatively correlated with integrated plasma response of GLP-1 (r=-0.75) in control experiments, implying that inhibition of fat absorption modifies determinants of gastric emptying of a meal. Orlistat administered similar to its use in obesity treatment accelerates gastric emptying of a solid mixed meal with a moderate energy load and profoundly attenuates release of GIP without appreciably altering plasma responses of CCK, GLP-1, and PP. Since GIP is being implemented in the development of obesity, its role in weight control attained by orlistat awaits further investigation.
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PMID:Orlistat accelerates gastric emptying and attenuates GIP release in healthy subjects. 1910 8

Obesity constitutes a major global healthcare challenge. The morbidity, mortality, and socioeconomic costs of obesity are considerable. No currently available medical therapy delivers substantial, sustainable weight loss. The need to better understand the mechanisms of appetite regulation is therefore clear. Over the last 20 years, peptide hormones released from the gastrointestinal tract in response to nutritional stimuli have come to be recognized as important physiological regulators of appetite. Hormones such as peptide YY, pancreatic polypeptide, glucagon-like peptide-1 and oxyntomodulin are thought to act as postprandial satiety signals. These physiological pathways of appetite control offer a promising basis for anti-obesity therapies. Here, we briefly review the state of current knowledge of these hormones' actions on brain appetite circuits, and prospects for future research and development.
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PMID:Gastrointestinal satiety signals. 1913 88

Bariatric surgery is the only effective treatment for patients with morbid obesity. This is no solution to the present obesity pandemic however. Currently licensed non-surgical pharmaceuticals are of limited efficacy and alternatives are needed. Harnessing the body's own appetite-regulating signals is a desirable pharmacological strategy. The gastrointestinal tract has a prime role in sensing and signalling food intake to the brain. Gut hormones are key mediators of this information, including: peptide YY (PYY), pancreatic polypeptide (PP), glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), ghrelin, amylin and cholecystokinin (CCK). This review summarises the latest knowledge regarding the physiological and pathophysiological role of gut hormones in regulating our food intake and how this knowledge could guide, or has guided, the development of weight-loss drugs. Up-to-date outcomes of clinical trials are evaluated and directions for the future suggested.
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PMID:Gut hormones: implications for the treatment of obesity. 1956 Apr 88

Obesity is one of the greatest public health challenges of the 21st century with 1.6 billion adults currently classified as being overweight and 400 million as obese. Obesity is causally associated with type 2 diabetes, hypertension, cardiovascular disease, obstructive sleep apnoea and certain forms of cancer and is now one of the leading causes of mortality and morbidity worldwide. The gastrointestinal tract is the largest endocrine organ in the body producing hormones that have important sensing and signaling roles in regulating body weight and energy expenditure. The last decade has witnessed a marked increase in our understanding of the role of gut hormones in energy homeostasis. Consequently, strategies aimed at modulating circulating gut hormone concentrations or targeting their receptors are being developed as potential pharmacotherapies for obesity. This review summarizes the current knowledge regarding the mechanisms, sites of action and effects of the anorectic gut hormones peptide tyrosine-tyrosine (PYY), pancreatic polypeptide (PP), oxyntomodulin, and amylin and of the unique orexigenic hormone, ghrelin.
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PMID:The role of gut hormones in the regulation of body weight and energy homeostasis. 1956 62

Our knowledge of the complex mechanisms underlying energy homeostasis has expanded enormously in recent years. Food intake and body weight are tightly regulated by the hypothalamus, brainstem and reward circuits, on the basis both of cognitive inputs and of diverse humoral and neuronal signals of nutritional status. Several gut hormones, including cholecystokinin, glucagon-like peptide-1, peptide YY, oxyntomodulin, amylin, pancreatic polypeptide and ghrelin, have been shown to play an important role in regulating short-term food intake. These hormones therefore represent potential targets in the development of novel anti-obesity drugs. This review focuses on the role of gut hormones in short- and long-term regulation of food intake, and on the current state of development of gut hormone-based obesity therapies.
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PMID:Obesity treatment: novel peripheral targets. 2000 77

Pancreatic polypeptide (PP) belongs to the neuropeptide Y (NPY) family of peptides and is released from pancreatic F cells postprandially. PP functions as a peptide hormone and has been associated with decreased food intake in humans and rodents. Our study describes the effects of PP on feeding behavior in dogs, whose mammalian order (Carnivora) is more distantly related to primates and rodents than these are to each other. Furthermore, obesity is becoming more prevalent in dogs which makes knowledge about their appetite regulation highly relevant. Repeated peripheral administration of physiological doses of PP (three injections of 30 pmol/kg each that were administered within 30 min) to six male beagle dogs prolonged the median time spent eating three servings of food by 19% but resulted in no reduction of food intake. In addition, PP decreased the duration of food-seeking behavior after the first serving by 71%. Thus, a physiological dose of PP seems to decrease both the appetitive and the consummatory drive in dogs.
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PMID:Peripheral administration of pancreatic polypeptide inhibits components of food-intake behavior in dogs. 2033 7

The World Health Organisation has estimated that by 2015 approximately 2.3 billion adults will be overweight and more than 700 million obese. Obesity is associated with an increased risk of diabetes, cardiovascular events, stroke and cancer. The hypothalamus is a crucial region for integrating signals from central and peripheral pathways and plays a major role in appetite regulation. In addition, there are reciprocal connections with the brainstem and higher cortical centres. In the arcuate nucleus of the hypothalamus, there are two major neuronal populations which stimulate or inhibit food intake and influence energy homeostasis. Within the brainstem, the dorsal vagal complex plays a role in the interpretation and relaying of peripheral signals. Gut hormones act peripherally to modulate digestion and absorption of nutrients. However, they also act as neurotransmitters within the central nervous system to control food intake. Peptide YY, pancreatic polypeptide, glucagon-like peptide-1 and oxyntomodulin suppress appetite, whilst ghrelin increases appetite through afferent vagal fibres to the caudal brainstem or directly to the hypothalamus. A better understanding of the role of these gut hormones may offer the opportunity to develop successful treatments for obesity. Here we review the current understanding of the role of gut hormones and the hypothalamus on food intake and body weight control.
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PMID:The role of gut hormones and the hypothalamus in appetite regulation. 2042 41


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