Low human peptide YY (PYY) plasma levels were recently reported to justify PYY replacement therapy in human obesity (N Engl J Med 2003 349(10) 941–948). The pharmacological potential of PYY 3–36 (mainly circulating form of PYY) is discussed controversially, as the influence of PYY in the regulation of energy balance remains unclear. Methods: PYY plasma levels of 51 lean (BMI: 22.7±0.5kg/m2), 20 anorectic (BMI: 15.2±0.2), 53 obese (BMI: 33.2±0.7) and 13 morbidly obese (BMI: 43.2±2.1) subjects were investigated. Additionally PYY levels from 13 obese patients before and after weight loss (-4.2%) and 20 anorectic patients before and after weight gain (+14%) were analyzed. PYY plasma levels were measured using a commercially available PYY EIA (Diagnostic Systems Laboratories, USA). Results: PYY levels in anorectic patients (92±8 pg/ml, p≤0.01) were higher than those of lean (43±4 pg/ml), obese (41±6 pg/ml) or morbidly obese (47±16 pg/ml) individuals. Weight gain in anorectic patients did not change fasting plasma PYY levels. PYY levels of obese patients decreased after weight loss (P≤0.001). Conclusion: Our findings from a large population of obese and morbidly obese patients indicate that there is no obvious PYY deficiency in human obesity. Therefore, a PYY replacement therapy does not seem to be an option for the treatment of obesity. In contrast, circulating PYY levels in humans might play a role in anorexia nervosa. However, until reliable methods for the specific quantification of PYY1–36 and PYY3–36 become available, findings regarding the functional role of endogenous PYY must be interpreted with caution.
