Peptide YY levels are elevated after gastric bypass surgery.

OBJECTIVE: Mechanisms that promote effective and sustained weight loss in persons who have undergone Roux-en-Y gastric bypass surgery are incompletely understood but may be mediated, in part, by changes in appetite. Peptide YY (PYY) is a gut-derived hormone with anorectic properties. We sought to determine whether gastric bypass surgery alters PYY levels or response to glucose.

RESEARCH METHODS AND PROCEDURES: PYY and ghrelin levels after a 75-gram oral glucose tolerance test were measured in 6 morbidly obese patients 1.5 +/- 0.7 (SE) years after gastric bypass compared with 5 lean and 12 obese controls.

RESULTS: After substantial body weight loss (36.8 +/- 3.6%) induced by gastric bypass, the PYY response to an oral glucose tolerance test was significantly higher than in controls (p = 0.01). PYY increased approximately 10-fold after a 75-gram glucose load to a peak of 303.0 +/- 37.0 pg/mL at 30 minutes (p = 0.03) and remained significantly higher than fasting levels for all subsequent time-points. In contrast, PYY levels in obese and lean controls increased to a peak of approximately 2-fold, which was only borderline significant. Ghrelin levels decreased in a symmetric but opposite fashion to that of PYY.

DISCUSSION: Gastric bypass results in a more robust PYY response to caloric intake, which, in conjunction with decreased ghrelin levels, may contribute to the sustained efficacy of this procedure. The findings provide further evidence for a role of gut-derived hormones in mediating appetite changes after gastric bypass and support further efforts to determine whether PYY(3-36) replacement could represent an effective therapy for obesity.