Effects of PYY[3-36] in rodent models of diabetes and obesity

BACKGROUND: Peptide YY (PYY) is a 36 amino-acid peptide secreted from ileal L cells following meals. The cleaved subpeptide PYY[3–36] is biologically active and may constitute the majority of circulating PYY-like immunoreactivity. The peptide family that includes PYY, pancreatic peptide and neuropep...

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Bibliographic Details
Published in:International Journal of Obesity 2004-08, Vol.28 (8), p.963-971
Main Authors: Pittner, R A, Moore, C X, Bhavsar, S P, Gedulin, B R, Smith, P A, Jodka, C M, Parkes, D G, Paterniti, J R, Srivastava, V P, Young, A A
Format: Article
Language:English
Subjects:
Biological and medical sciences
Body weight
Complications and side effects
Diabetes
Diet
Epidemiology
Food
Health aspects
Health Promotion and Disease Prevention
Internal Medicine
Ligands
Medical sciences
Medicine
Medicine & Public Health
Metabolic Diseases
Metabolic disorders
Mice
Neuropeptides
Obesity
Peptides
Polypeptides
Public Health
Risk factors
Rodents
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Summary:BACKGROUND: Peptide YY (PYY) is a 36 amino-acid peptide secreted from ileal L cells following meals. The cleaved subpeptide PYY[3–36] is biologically active and may constitute the majority of circulating PYY-like immunoreactivity. The peptide family that includes PYY, pancreatic peptide and neuropeptide Y is noted for its orexigenic effect following intracerebroventricular administration. OBJECTIVE: To investigate the effects of peripheral (intraperitoneal and chronic subcutaneous) infusions of PYY[3–36] on food intake, body weight and glycemic indices. DESIGN/RESULTS: Food intake was measured in normal mice and in several rodent models of obesity and type II diabetes. In marked contrast to the reported central orexigenic effects, in the present study, PYY[3–36] acutely inhibited food intake by up to 45%, with an ED 50 of 12.5 μg/kg in fasted female NIH/Swiss mice. A 4-week infusion reduced weight gain in female ob/ob mice, without affecting the cumulative food intake. In diet-induced obese male mice, PYY[3–36] infusion reduced cumulative food intake, weight gain and epididymal fat weight (as a fraction of carcass) with similar ED 50 's (466, 297 and 201 μg/kg/day, respectively) and prevented a diet-induced increase in HbA1c. Infusion at 100 μg/kg/day for 8 weeks in male fa/fa rats reduced the weight gain (288±11 vs 326±12 g in saline-infused controls; P
ISSN:0307-0565
1476-5497
DOI:10.1038/sj.ijo.0802696