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Gut Jul 2003Obesity is a growing epidemic, causally associated with a number of serious medical conditions, including diabetes mellitus, coronary heart disease, and several cancers....
Obesity is a growing epidemic, causally associated with a number of serious medical conditions, including diabetes mellitus, coronary heart disease, and several cancers. The gut hormones ghrelin and peptide YY are secreted from the gut in response to changes to nutritional status. While food intake is stimulated by ghrelin, it is inhibited by peptide YY. The discovery, anatomy, and physiology of ghrelin and peptide YY are discussed, focusing on the adaptive changes in diseases such as obesity and anorexia nervosa. Ghrelin and PYY are important therapeutic targets in the quest to find an effective antiobesity treatment.
Topics: Appetite; Body Weight; Eating; Fasting; Gastric Bypass; Ghrelin; Humans; Hypothalamus; Obesity, Morbid; Peptide Hormones; Peptide YY
PubMed: 12801943
DOI: 10.1136/gut.52.7.918 -
Neuropeptides Dec 2012The gut-brain axis refers to the bidirectional communication between the gut and the brain. Four information carriers (vagal and spinal afferent neurons, immune... (Review)
Review
The gut-brain axis refers to the bidirectional communication between the gut and the brain. Four information carriers (vagal and spinal afferent neurons, immune mediators such as cytokines, gut hormones and gut microbiota-derived signalling molecules) transmit information from the gut to the brain, while autonomic neurons and neuroendocrine factors carry outputs from the brain to the gut. The members of the neuropeptide Y (NPY) family of biologically active peptides, NPY, peptide YY (PYY) and pancreatic polypeptide (PP), are expressed by cell systems at distinct levels of the gut-brain axis. PYY and PP are exclusively expressed by endocrine cells of the digestive system, whereas NPY is found at all levels of the gut-brain and brain-gut axis. The major systems expressing NPY comprise enteric neurons, primary afferent neurons, several neuronal pathways throughout the brain and sympathetic neurons. In the digestive tract, NPY and PYY inhibit gastrointestinal motility and electrolyte secretion and in this way modify the input to the brain. PYY is also influenced by the intestinal microbiota, and NPY exerts, via stimulation of Y1 receptors, a proinflammatory action. Furthermore, the NPY system protects against distinct behavioural disturbances caused by peripheral immune challenge, ameliorating the acute sickness response and preventing long-term depression. At the level of the afferent system, NPY inhibits nociceptive input from the periphery to the spinal cord and brainstem. In the brain, NPY and its receptors (Y1, Y2, Y4, Y5) play important roles in regulating food intake, energy homeostasis, anxiety, mood and stress resilience. In addition, PP and PYY signal to the brain to attenuate food intake, anxiety and depression-related behaviour. These findings underscore the important role of the NPY-Y receptor system at several levels of the gut-brain axis in which NPY, PYY and PP operate both as neural and endocrine messengers.
Topics: Animals; Brain; Gastrointestinal Hormones; Gastrointestinal Tract; Homeostasis; Humans; Immune System; Neuropeptide Y; Pancreatic Polypeptide; Peptide YY; Signal Transduction
PubMed: 22979996
DOI: 10.1016/j.npep.2012.08.005 -
Physiological Reports Sep 2022Severe systemic inflammation is associated with nausea, loss of appetite, and delayed gastric emptying, which increases hospitalization admission length and mortality... (Randomized Controlled Trial)
Randomized Controlled Trial
Severe systemic inflammation is associated with nausea, loss of appetite, and delayed gastric emptying, which increases hospitalization admission length and mortality rate. There is a lack of human controlled studies exploring gastric emptying rates and underlying mechanisms during inflammatory conditions. We aimed to investigate if systemic inflammation in young men delays gastro-intestinal transit times, lowers motility, and affects gastrointestinal hormone secretion. This substudy of a randomized crossover trial investigated eight healthy young men on two separate occasions; (I) following an overnight fast (healthy conditions/HC) and (II) fasting and bedrest combined with two lipopolysaccharide (LPS) injections of 1 ng kg following an overnight fast and 0.5 ng kg following another 24 h (systemic inflammation/SI). A standardized protein beverage and a SmartPill capsule (a wireless gastrointestinal monitoring system) were swallowed during each occasion. Whole gut transit time was comparable between HC and SI. SI decreased gastric mean pressure peak amplitude (p = 0.04) and increased pH rise across the pylorus and small bowel pH (p = 0.02) compared with HC. Glucagon-like peptide-1 was elevated during SI compared with HC (p = 0.04). Peptide YY was lower during SI compared with HC (p = 0.007). Prolonged LPS exposure combined with fasting and bedrest elevated glucagon-like peptide 1 concentrations, which may play a role for the nausea and loss of appetite typically associated with SI.
Topics: Cross-Over Studies; Gastrointestinal Hormones; Gastrointestinal Motility; Glucagon-Like Peptide 1; Humans; Inflammation; Lipopolysaccharides; Male; Nausea; Peptide YY
PubMed: 36117310
DOI: 10.14814/phy2.15462 -
American Journal of Physiology.... Jul 2007
Topics: Animals; Eating; Gastric Emptying; Insulin Resistance; Mice; Peptide Fragments; Peptide YY; Rats; Weight Gain
PubMed: 17491108
DOI: 10.1152/ajpregu.00311.2007 -
American Journal of Physiology.... Nov 2007
Topics: Animals; Anti-Obesity Agents; Eating; Humans; Male; Mice; Obesity; Peptide YY
PubMed: 17848627
DOI: 10.1152/ajpendo.00568.2007 -
Biological Psychology Jan 2018Ghrelin and peptide YY (PYY) during ad libitum smoking have been associated with decreased reported craving (ghrelin) and increased positive affect (PYY), and higher...
Ghrelin and peptide YY (PYY) during ad libitum smoking have been associated with decreased reported craving (ghrelin) and increased positive affect (PYY), and higher baseline ghrelin levels predicted subsequent increased risk of smoking relapse. The current study assessed PYY and ghrelin during ad libitum smoking and again after the initial 48h of a smoking cessation attempt. The data compared smokers who abstained for 28days (n=37), smokers who relapsed (n=54), and nonsmokers (n=37). Plasma samples and subjective measures assessing craving and mood were collected at the beginning of each session. Results showed that relapsers experienced greater levels of distress (ps <0.01). While nonsmokers and abstainers showed no change in ghrelin across the initial 48h, relapsers declined (p <0.01). With PYY, relapsers increased (p <0.05) across the early abstinent phase. PYY and ghrelin may be useful predictors of relapse, specifically in reference to early withdrawal.
Topics: Adult; Craving; Female; Ghrelin; Humans; Male; Peptide YY; Recurrence; Smoking; Smoking Cessation; Stress, Psychological
PubMed: 28300626
DOI: 10.1016/j.biopsycho.2017.03.007 -
International Journal of Molecular... Feb 2013Peptide YY (PYY) is affected in several gastrointestinal diseases and disorders. Changes in PYY appear to be an adaptive response to alterations in pathophysiological... (Review)
Review
Peptide YY (PYY) is affected in several gastrointestinal diseases and disorders. Changes in PYY appear to be an adaptive response to alterations in pathophysiological conditions caused by the disease. This applies to gastrointestinal diseases/disorders such as irritable bowel syndrome, inflammatory bowel disease, celiac disease, systemic sclerosis, and post-intestinal resection. By contrast, the changes in PYY in chronic idiopathic slow transit constipation (CST) seem to be of a primary nature, and may be one etiological factor of the disease. Abnormalities in PYY seem to contribute to the development of symptoms present in irritable bowel syndrome, inflammatory bowel disease, gastroenteropathy in long-standing diabetes and CST. The changes in PYY could, however, be favorable in some gastrointestinal disorders such as celiac disease, systemic sclerosis and post-intestinal resection state. Investigating changes in PYY in gastrointestinal diseases/disorders could be beneficial in clinical practice, where a receptor agonist or an antagonist can be used as a drug, depending on the condition. Similar to other neuroendocrine peptides/amines of the gut, PYY has broad physiological/pharmacological effects: it can bind to and activate several receptors with independent actions. Thus, in order to use PYY as a drug, receptor-specific agonists or antagonists need to be developed.
Topics: Animals; Drug Discovery; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Tract; Humans; Peptide YY
PubMed: 23292145
DOI: 10.3892/ijmm.2012.1222 -
Endocrinology Apr 2018The lipid sensor G protein-coupled receptor 119 (GPR119) is highly expressed by enteroendocrine L-cells and pancreatic β-cells that release the hormones, peptide YY...
The lipid sensor G protein-coupled receptor 119 (GPR119) is highly expressed by enteroendocrine L-cells and pancreatic β-cells that release the hormones, peptide YY (PYY) and glucagonlike peptide 1, and insulin, respectively. Endogenous oleoylethanolamide (OEA) and the dietary metabolite, 2-monoacylglycerol (2-OG), can each activate GPR119. Here, we compared mucosal responses with selective, synthetic GPR119 agonists (AR440006 and AR231453) and the lipids, OEA, 2-OG, and N-oleoyldopamine (OLDA), monitoring epithelial ion transport as a readout for L-cell activity in native mouse and human gastrointestinal (GI) mucosae. We also assessed GPR119 modulation of colonic motility in wild-type (WT), GPR119-deficient (GPR119-/-), and PYY-deficient (PYY-/-) mice. The water-soluble GPR119 agonist, AR440006 (that cannot traverse epithelial tight junctions), elicited responses, when added apically or basolaterally in mouse and human colonic mucosae. In both species, GPR119 responses were PYY, Y1 receptor mediated, and glucose dependent. AR440006 efficacy matched the GI distribution of L-cells in WT tissues but was absent from GPR119-/- tissue. OEA and 2-OG responses were significantly reduced in the GPR119-/- colon, but OLDA responses were unchanged. Alternative L-cell activation via free fatty acid receptors 1, 3, and 4 and the G protein-coupled bile acid receptor TGR5 or by the melanocortin 4 receptor, was unchanged in GPR119-/- tissues. The GPR119 agonist slowed transit in WT but not the PYY-/- colon in vitro. AR440006 (intraperitoneally) slowed WT colonic and upper-GI transit significantly in vivo. These data indicate that luminal or blood-borne GPR119 agonism can stimulate L-cell PYY release with paracrine consequences and slower motility. We suggest that this glucose-dependent L-cell response to a gut-restricted GPR119 stimulus has potential therapeutic advantage in modulating insulinotropic signaling with reduced risk of hypoglycemia.
Topics: Animals; Colon; Dopamine; Endocannabinoids; Gastrointestinal Motility; Glucose; Humans; Intestinal Mucosa; Ion Transport; Mice; Mice, Knockout; Monoglycerides; Oleic Acids; Oxadiazoles; Peptide YY; Pyrimidines; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 29471473
DOI: 10.1210/en.2017-03172 -
Neuropeptides Feb 2022Control of appetite and feed intake in fish larvae are still largely unexplored. Two of the key players in controlling vertebrate's feed intake are cholecystokinin (CCK)...
Control of appetite and feed intake in fish larvae are still largely unexplored. Two of the key players in controlling vertebrate's feed intake are cholecystokinin (CCK) and peptide YY (PYY). Here we investigated the mRNA expression of pyy, cck and cck receptors (cckr) in the brain (head) and gut of Atlantic halibut larvae in response to three consecutive meals. We used Artemia nauplii cysts that are commonly ingested by halibut larvae when present as inert feed, and three water-soluble extracts as attractants to stimulate appetite. Cyst intake was not affected by the use of attractants and overall ingestion rate was low. Differences in mRNA expression of cck and pyy were observed between the halibut larvae that had eaten and those that had not despite readily available feed (cysts), supporting that mechanisms for control of feed intake are at least partly functional. All genes analysed were present in the brain and gut, however the different expression profiles between paralogues suggest potential divergent functions. In the gut, cck2 and pyyb mRNA expression was significantly higher in the larvae that ate cysts compared to larvae that decided to not eat, indicating that these genes play a satiety function in the halibut larvae similar to the general vertebrate scheme. However, cck2, cck2r1, and pyy mRNA expression in the brain were lower in the fed-filled larvae group compared to larvae before eating, which contrasts with the presumable anorectic function of these genes. Further research is required to fully evaluate how PYY and CCK affect the feeding biology in halibut larvae, contributing to formulate inert diets that can stimulate appetite and feed intake.
Topics: Animals; Appetite; Brain; Cholecystokinin; Eating; Flounder; Gastrointestinal Tract; Peptide YY; Receptors, Cholecystokinin
PubMed: 34741845
DOI: 10.1016/j.npep.2021.102202 -
American Journal of Physiology.... May 2019A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole...
A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3.5- and 2.9-fold, respectively. Furthermore, we find that responses depend on BA absorption followed by basolateral activation of the BA-receptor Takeda-G protein-coupled-receptor 5. Surprisingly, the apical sodium-dependent BA transporter, which serves to absorb conjugated BAs, was not required for colonic conjugated BA absorption or conjugated BA-induced peptide secretion. In conclusion, we demonstrate that BAs represent a major physiological stimulus for colonic L-cell secretion. By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion. The study provides convincing evidence that basolateral Takeda-G protein-coupled-receptor 5 activation is mediating the effects of bile acids in the colon and thus add to the existing literature described for L cells in the ileum.
Topics: Animals; Bile Acids and Salts; Carrier Proteins; Colon; Glucagon-Like Peptide 1; Ileum; Intestinal Absorption; L Cells; Membrane Glycoproteins; Mice; Peptide YY; Rats
PubMed: 30767682
DOI: 10.1152/ajpgi.00010.2019