Peptide YY (PYY) is a gut hormone secreted by colonic L cells that functions as a key regulator of appetite, metabolism, and gastrointestinal physiology 1. PYY mediates its effects primarily through Y2 receptor activation in the hypothalamus to suppress food intake and promote satiety 2. The hormone is released from distal gut in response to nutrient ingestion and acts as a postprandial satiety signal 1. Beyond appetite suppression, PYY exhibits broader metabolic and protective functions. It improves pancreatic beta-cell survival and function through Y1 receptor activation, with therapeutic implications for diabetes management 2. PYY also attenuates colonic inflammation via neural pathways and demonstrates antitrophic properties in the pancreas by decreasing cytokine and amylase release 34. The hormone's secretion from human enteroendocrine L cells shows site-specific variation, with greater release in distal colon regions and declining production with age 5. Clinically, PYY elevation represents a therapeutic target for obesity management. Interventions increasing colonic propionate or inhibiting MGAT2 increase plasma PYY levels, reduce energy intake, and prevent weight gain in humans 67. These findings position PYY-based therapeutics as promising approaches for obesity, metabolic dysfunction, and gastrointestinal inflammation management.