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

Abstract

Peptide YY ] 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 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. Diabetes 54: 3198 -3204, 2005 T he rising prevalence of obesity in the U.S. and other countries (1,2) is linked to increases in the incidence of obesity-related diseases (diabetes, cardiovascular disease, hypertension, and cancer), elevated health care costs, and reduced quality of life (3,4). The success of pharmacological intervention to reverse trends in obesity demographics depends on a better understanding of the physiology of appetite and body weight regulation. Because of their involvement in the regulation of energy homeostasis, hypothalamic and brainstem systems are major targets for pharmacological treatment of obesity (5,6).The arcuate nucleus of the hypothalamus (ARH) contains two cell types that act antagonistically to regulate energy intake and expenditure: activation of cells that express proopiomelanocortin produces anorectic effects, whereas activation of cells that produce neuropeptide Y (NPY) elicits feeding and energy conservation (7). Ingestion of nutrients causes L-cells in the gastrointestinal tract to release PYY , which is an endogenous ligand for several NPY receptors (Y1, Y2, and Y5) (8). However, a cleavage product of PYY , PYY , is relatively selective for the NPY Y2 receptor (9). The NPY Y2 receptor is expressed in the ARH and other sites and is the dominant inhibitory autoreceptor on NPY neurons (10,11). Evidence of a nonsaturable transport mechanism for PYY across the blood-brain barrier (12), coupled with recent data by Riediger et al. (13) that physiological doses of PYY (1-36) induced c-Fos in the ARH but not the area postrema (in the hindbrain), support the hypothesis that circulating PYY is thought to suppress appetite through inhibition of ARH NPY neurons, but this does not exclude other possible sites of action.Peripheral PYY administration reduces food intake in humans and rodents (14 -16). Although the effects of PYY on gastric emptying are reproducible (17-19), the effectiveness of ...

Role of gastrointestinal hormones in feeding behavior and obesity treatment

“…Peripheral administration of PYY in rodents decreased appetite and food intake [66][67][68], and also reduced body weights in other experimental animals [69,70]. In human, intravenous infusion of PYY 3-36 also showed the same results, indicating the role of PYY as an anorexigenic peptide [71].…”

Adult-onset PYY overexpression in mice reduces food intake and increases lipogenic capacity

“…Acute peripheral administration of PYY3-36 has been demonstrated to reduce food intake in both lean and obese animals and humans (Batterham et al, 2002, Pittner et al, 2004, Koegler et al, 2005, le Roux et al, 2006and Field et al, 2010. In diet-induced obese rodents, PYY3-36 has also been shown to promote lipid oxidation and/or reduce lipogenesis (Adams et al, 2006 andvan den Hoek et al, 2007), as well as to enhance insulin-mediated glucose disposal (van den Hoek et al, 2004, van den Hoek et al, 2007, Boey et al, 2006aand Boey et al, 2006b, further demonstrating the potential therapeutic value of PYY3-36 in the treatment of obesity and type-2 diabetes.…”

PYY(3–36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity

“…Briefly, a 0.25 mg/ml solution of PYY(3-36) was prepared in saline and stored at 37°C. From this solution, samples were taken at days 1,3,7,8,10,11,14,16,18,21,23, and 25. Degradation was stopped by precipitation of sample with 10 l of 50:50 (vol/vol) MeCN-trifluoroacetic acid.…”