What is Peptide YY (PYY)?

Peptide YY (PYY): A Gut Hormone Regulating Appetite and Metabolism

Peptide YY (PYY) is a 36-amino acid gut hormone primarily secreted by L-cells in the distal gastrointestinal tract that functions as an appetite suppressant, decreases food intake, delays gastric emptying, and plays an important role in energy homeostasis and glucose regulation. 1, 2

Structure and Forms

• PYY belongs to the Neuropeptide Y Family of Peptides (also called Pancreatic Polypeptide-Fold Family)
• Two main circulating forms:
  • PYY(1-36): The full-length peptide (~60% of circulating PYY)
  • PYY(3-36): Formed when dipeptidyl peptidase IV (DPP-IV) cleaves the N-terminal tyrosine-proline residues (~40% of circulating PYY) 2

Physiological Functions

Appetite and Food Intake Regulation

• PYY(3-36) is a potent anorexigenic hormone (reduces appetite) 3
• Acts primarily through Y2 receptors in the arcuate nucleus of the hypothalamus
• Inhibits NPY neurons, which normally stimulate appetite 2, 4
• PYY levels:
  • Increase by approximately 50% after meals, proportional to caloric content 5, 4
  • Decrease to 40-60% of baseline during fasting 5
  • Peak approximately 1 hour after food intake 4

Gastrointestinal Functions

PYY inhibits multiple digestive functions:

• Gastric acid secretion
• Gastric emptying
• Small bowel and colonic chloride secretion
• Mouth to cecum transit time
• Pancreatic exocrine secretion
• Pancreatic insulin secretion 2

Other Physiological Effects

• Promotes postprandial naturesis
• Elevates systolic and diastolic blood pressure
• Contributes to islet cell development and pancreatic cell regeneration 1, 2

Clinical Significance

Obesity

• PYY levels are lower in overweight individuals 3
• May play a primary role in appetite suppression and weight loss observed after bariatric surgery 2
• PYY(3-36) administration reduces food intake in both rodents and humans 4

Type 2 Diabetes

• PYY has potential as a treatment for type 2 diabetes due to its ability to:
  • Delay gastric emptying
  • Reduce appetite
  • Decrease weight
  • Lower blood glucose 6

Therapeutic Challenges

• Clinical use is limited by:
  • Rapid clearance by kidneys
  • Enzymatic degradation
  • Short half-life 6
• Current research focuses on structural modifications to enhance stability and biological activity:
  • Amino acid substitution
  • PEGylation
  • Lipidation
  • Fusion with other proteins 6

Regulation of PYY

Stimulators of PYY Release

• Intraluminal nutrients:
  • Glucose
  • Bile salts
  • Lipids
  • Short-chain fatty acids
  • Amino acids
• Regulatory peptides:
  • Cholecystokinin (CCK)
  • Vasoactive intestinal polypeptide (VIP)
  • Gastrin
  • GLP-1 2

Independence from Leptin

• PYY regulation is independent of leptin in the short term
• Administration of recombinant human leptin at both physiological and pharmacological doses does not affect PYY levels 5

PYY in Special Populations

Type 1 Diabetes

• Limited data available
• In children with T1D, PYY levels were unchanged compared to healthy controls 1

Bariatric Surgery Patients

• PYY plays a significant role in the appetite suppression and weight loss observed after bariatric operations 2
• Changes in gut hormones including PYY are part of the mechanisms underlying the beneficial effects of bariatric surgery 1

Clinical Implications

The understanding of PYY's role in appetite regulation and energy homeostasis has important implications for developing new therapeutic approaches for obesity and diabetes. Current research is focused on developing PYY analogs with improved pharmacokinetic properties to overcome the limitations of the native hormone for clinical use 6.