Peptide YY(3–36) Inhibits Morning, but Not Evening, Food Intake and Decreases Body Weight in Rhesus Macaques

doi:10.2337/diabetes.54.11.3198

Peptide YY_(3–36) Inhibits Morning, but Not Evening, Food Intake and Decreases Body Weight in Rhesus Macaques

¹Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon
²Division of Reproductive Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon

Address correspondence and reprint requests to Michael Cowley, PhD, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave., Beaverton, OR 97006. E-mail: cowleym{at}ohsu.edu

Abstract

Peptide YY_(3–36) [PYY_(3–36)] is a hormone that is released after meal ingestion that is currently being investigated for the treatment of obesity; however, there are conflicting reports of the effects of PYY_(3–36) on energy balance in rodent models. To shed light on this controversy, we studied the effect of PYY_(3–36) on food intake and body weight in a nonhuman primate. Intravenous PYY_(3–36) infusions before a morning meal transiently suppressed the rate of food intake but did not suppress the evening meal or 24-h intake. Twice-daily or continuous intravenous PYY_(3–36) infusions to supraphysiological levels (levels that exceeded normal physiological levels) again suppressed the rate of feeding for the morning but not the evening meal. Twice-daily intravenous PYY_(3–36) infusions for 2 weeks significantly decreased body weight in all test animals (average weight loss 1.9%) without changing insulin response to glucose infusion. These results show that endogenous PYY_(3–36) may alter morning but not evening meal intake, and supraphysiological doses are required for effective suppression of food intake.