Peptide YY (3-36) human

Peptide YY (PYY) is a 36 amino acid, straight chain polypeptide, which is co-localized with GLP-1 in the L-type endocrine cells of the GI mucosa. PYY shares structural homology with neuropeptide Y (NPY) and pancreatic polypeptide (PP), and together form the Neuropeptide Y Family of Peptides, which is also called the Pancreatic Polypeptide-Fold Family of Peptides. PYY release is stimulated by intraluminal nutrients, including glucose, bile salts, lipids, short-chain fatty acids and amino acids. Regulatory peptides such as cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), gastrin and GLP-1 modulate PYY release. The proximal GI tract may also participate in the regulation of PYY release through vagal fibers. After release, dipeptidyl peptidase IV (DPP-IV; CD 26) cleaves the N-terminal tyrosine-proline residues forming PYY(3-36). PYY(1-36) represents about 60% and PYY(3-36) 40% of circulating PYY. PYY acts through Y-receptor subtypes: Y1, Y2, Y4 and Y5 in humans. PYY(1-36) shows high affinity to all four receptors while PYY(3-36) is a specific Y2 agonist. PYY inhibits many GI functions, including gastric acid secretion, gastric emptying, small bowel and colonic chloride secretion, mouth to cecum transit time, pancreatic exocrine secretion and pancreatic insulin secretion. PYY also promotes postprandial naturesis and elevates systolic and diastolic blood pressure. PYY(1-36) and PYY(3-36) cross the blood-brain barrier and participate in appetite and weight control regulation. PYY(1-36) acting through Y1- and Y5-receptors increases appetite and stimulates weight gain. PYY(3-36) acting through Y2-receptors on NPY-containing cells in the arcuate nucleus inhibits NPY release and, thereby, decreases appetite and promotes weight loss. PYY may play a primary role in the appetite suppression and weight loss observed after bariatric operations.

Purpose:The gut-brain axis could be a possible key factor in the pathophysiology of anorexia nervosa. The neuropeptide peptide YY3-36, secreted by endocrine L cells of the gastrointestinal tract, is a known regulator of appetite and food intake. The objective of this study was to investigate peptide YY3-36plasma concentrations at different stages of anorexia nervosa in a combined cross-sectional and longitudinal design to differentiate between effects of acute undernutrition and more enduring characteristics.Methods:We measured fasting plasma peptide YY3-36concentrations in young patients with acute anorexia nervosa (n = 47) and long-term recovered patients (n = 35) cross-sectionally in comparison to healthy control participants (n = 58), and longitudinally over the course of inpatient treatment. Physical activity was controlled as it may modulate peptide YY secretion.Results:There was no group difference in peptide YY3-36concentration among young acutely underweight anorexia nervosa patients, long-term recovered anorexia nervosa patients, and healthy control participants. Longitudinally, there was no change in peptide YY3-36concentration after short-term weight rehabilitation. For acute anorexia nervosa patients at admission to treatment, there was a negative correlation between peptide YY3-36concentration and body mass index.Conclusions:The current study provides additional evidence for a normal basal PYY3-36concentration in AN. Future studies should study multiple appetite-regulating peptides and their complex interplay and also use research designs including a food challenge.

Peptide YY (PYY) is secreted as a 36 amino acid, straight chain polypeptide, and is found in greatest concentrations in the terminal ileum, colon and rectum. After secretion, dipeptidyl peptidase IV (DPP-IV) cleaves the N-terminal Tyrosine-Proline residues from PYY(1-36), producing PYY(3-36). PYY(1-36) acts at all four human Y receptors, Y1, Y2, Y4 and Y5, while PYY(336) is a specific Y2 receptor agonist. PYY participates in the regulation of appetite and weight balance through hypothalamic-based mechanisms. PYY(1-36) stimulates appetite and weight gain through Y1 and Y5 receptors. PYY(3-36) suppresses appetite and stimulates weight loss through Y2 receptors. GI diseases that cause malabsorption increase both basal and meal-stimulated PYY levels. In contrast, obesity decreases both basal and meal-stimulated PYY levels. Mutations in the human PYY and Y2 receptor genes may contribute to the development of obesity. Small bowel resection elevates PYY levels in humans. Colon resections increase PYY levels in animal models but not in man. PYY changes following bariatric operations are incompletely studied. Vertical banded gastroplasty, open Roux-en-Y gastric bypass and jejunoileal bypass significantly elevate basal and meal-stimulated PYY levels. In dogs with Pavlov pouches, Roux-en-Y duodenojejunostomy (duodenal switch) increases PYY levels compared to Roux-en-Y gastrojejunostomy. DPP-IV activity is increased in obese individuals and remains increased after biliopancreatic diversion. Thus, diseases or operations which cause malabsorption, elevate basal and meal-stimulated PYY levels. Bariatric operations also increase basal and meal-stimulated PYY levels. This suggests that the combination of increased PYY levels and elevated levels of DPP-IV observed after bariatric operations may generate increased circulating levels of PYY(3-36), leading to hypothalamic-mediated suppression of appetite and promotion of weight loss through Y2 receptor mediated mechanisms.