Original Article
International Journal of Obesity (2006) 30, 68–72. doi:10.1038/sj.ijo.0803067; published online 20 September 2005
Lower mean weight after 14 days intravenous administration peptide YY3–36 (PYY3–36) in rabbits
A P Sileno1, G C Brandt1, B M Spann1 and S C Quay1
1Nastech Pharmaceutical Company Inc., Bothell, WA, USA
Correspondence: BM Spann, Nastech Pharmaceutical Company Inc., 3450 Monte Villa Parkway, Bothell, WA 98021, USA. E-mail: bspann@nastech.com
Received 4 August 2004; Revised 29 June 2005; Accepted 17 July 2005; Published online 20 September 2005.
Abstract
Objective:
Endogenous peptide YY3–36 (PYY3–36) is associated with postprandial regulation of appetite. We investigated the safety and effectiveness of peripherally administered synthetic human PYY3–36 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 PYY3–36 bolus at 4.1, 41.0, or 205 
g/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 PYY3–36 205 g/kg animals was conducted. All animals were subject to clinical and macroscopic observation.
Results:
The trend effect of higher dose PYY3–36 on lower average weight was significant (P=0.01; Day 14 compared to baseline) and its effect on reduced food consumption was suggested (P=0.065; number of days 
75% 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 PYY3–36 (205 g/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.
Keywords:
peptide YY3–36, PYY3–36, gastrointestinal hormone, satiety, radioimmunoassay
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
RESEARCH
The paradox of the renin-angiotensin system in chronic renal disease
Kidney International Original Article
