Lower mean weight after 14 days intravenous administration peptide YY3–36 (PYY3–36) in rabbits

Abstract

Objective: Endogenous peptide YY ) is associated with postprandial regulation of appetite. We investigated the safety and effectiveness of peripherally administered synthetic human PYY 3-36 for 14 days in New Zealand white rabbits. Weight gain and food consumption were assessed and pharmacokinetics and toxicity characterized. Research methods and procedures: In all, 24 animals were randomized to one of four intravenous treatment groups -control (0.9% saline) or PYY 3-36 bolus at 4.1, 41.0, or 205 mg/kg/day. Body weight and consumption of fixed food allotment were measured daily. Hematology and serum chemistries were profiled at baseline and Day 15, and pharmacokinetics measured following dose 14. Histopathologic examination of designated tissues and organs in control and PYY 3-36 205 mg/kg animals was conducted. All animals were subject to clinical and macroscopic observation. Results: The trend effect of higher dose PYY 3-36 on lower average weight was significant (P ¼ 0.01; Day 14 compared to baseline) and its effect on reduced food consumption was suggested (P ¼ 0.065; number of days p75% food eaten, compared with control). Hematology and clinical chemistries were within normal limits pretest and at Day 15. No clinical, macroscopic, histologic, or microscopic changes related to the test article were observed over the course of study. Discussion: Lower average weight occurs in rabbits treated once daily with intravenous injection PYY 3-36 (205 mg/kg/day) over 14 days. No clinical or histologic signs of toxicity were observed. Further research is warranted to describe alternate routes of peripheral administration for optimizing weight control.

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].…”

A Novel Long-Acting Selective Neuropeptide Y2 Receptor Polyethylene Glycol-Conjugated Peptide Agonist Reduces Food Intake and Body Weight and Improves Glucose Metabolism in Rodents

“…PYY(3-36) reduces acute food intake in lean, DIO, ob/ob, and db/db mice, and in rats, rabbits, and monkeys, and daily administration of PYY(3-36) causes body weight loss in DIO and ob/ob mice, rats, and rabbits (Batterham et al, 2002;Challis et al, 2003;Cox and Randich, 2004;Halatchev et al, 2004;Pittner et al, 2004;Abbott et al, 2005;Chelikani et al, 2005;Koegler et al, 2005;Moran et al, 2005;Neary et al, 2005;Adams et al, 2006;Sileno et al, 2006;Vrang et al, 2006). PYY(3-36) does not reduce food intake in NPY2 knockout mice, or when it is coadministered with the NPY2 antagonist BIIE0246 in wild-type rats, suggesting that the anorexigenic effect of PYY(3-36) is mediated specifically through the NPY2 receptor (Batterham et al, 2002;Abbott et al, 2005).…”

Gastrointestinal satiety signals

“…Although there was initially some contention regarding the effects of PYY 3À36 on energy intake in animal models, 24 a number of research groups have demonstrated that peripheral PYY 3À36 inhibits food intake and reduces body weight gain in several species. [25][26][27][28][29][30] In the first study of the effects of PYY 3À36 on food intake in humans, spontaneous food intake was reduced by 30% at plasma levels similar to those seen physiologically. 25 A further recent study observed a dosedependent reduction in appetite and food intake in response to intravenous PYY 3À36 administration in normal weight volunteers, although nausea occurred at higher doses.…”