Document Detail

Effects of exendin-4 alone and with peptide YY(3-36) on food intake and body weight in diet-induced obese rats.
MedLine Citation:
PMID:  20559304     Owner:  NLM     Status:  MEDLINE    
Significant weight loss following Roux-en-Y gastric bypass surgery (RYGB) in obese humans correlates with enhanced secretion of anorexigenic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY(3-36) (PYY(3-36)). Our aim here was to identify a dosing strategy for intraperitoneal (IP) infusion of GLP-1 homologue exendin-4 alone and with PYY(3-36) that produces a sustained reduction in daily food intake and body weight in diet-induced obese (DIO) rats. We tested 12 exendin-4 strategies over 10 weeks. Exendin-4 infused during the first and last 3 h of the dark period at 15-20 pmol/h (0.15 nmol/kg/day) produced a sustained 24 ± 1% reduction in daily food intake for 17 days, and decreased body weight by 7%. In a separate group of DIO rats, none of seven dosing strategies combining exendin-4 and PYY(3-36) produced a similar reduction in daily food intake for >10 days. The subsequent decline in efficacies of exendin-4 alone and with PYY(3-36) on food intake and body weight in each experiment suggested possible receptor downregulation and tolerance to treatments. However, when treatments were discontinued for 1 day following losses in efficacies, daily food intake significantly increased. Together, these results demonstrate that (i) intermittent IP infusion of a low dose of exendin-4 can produce a relatively prolonged reduction in daily food intake and body weight in DIO rats, (ii) co-infusion of exendin-4 and PYY(3-36) does not further prolong this response, and (iii) activation of an orexigenic mechanism gradually occurs to counteract the inhibitory effects of exendin-4 alone and with PYY(3-36) on food intake and body weight.
Roger D Reidelberger; Alvin C Haver; Bettye A Apenteng; Krista L Anders; Sharalyn M Steenson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-06-17
Journal Detail:
Title:  Obesity (Silver Spring, Md.)     Volume:  19     ISSN:  1930-739X     ISO Abbreviation:  Obesity (Silver Spring)     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-28     Completed Date:  2011-05-04     Revised Date:  2012-08-13    
Medline Journal Info:
Nlm Unique ID:  101264860     Medline TA:  Obesity (Silver Spring)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  121-7     Citation Subset:  IM    
Department of Veterans Affairs, Nebraska Western Iowa Health Care System, Omaha, Nebraska, USA.
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MeSH Terms
Body Weight / drug effects*,  physiology
Diet / adverse effects
Dose-Response Relationship, Drug
Drug Combinations
Drug Evaluation, Preclinical
Eating / drug effects*,  physiology
Hypoglycemic Agents / administration & dosage,  pharmacology
Obesity / drug therapy,  etiology,  physiopathology*
Peptide YY / administration & dosage*,  pharmacology
Peptides / administration & dosage*,  pharmacology*
Rats, Sprague-Dawley
Venoms / administration & dosage*,  pharmacology*
Weight Loss / drug effects
Grant Support
Reg. No./Substance:
0/Drug Combinations; 0/Hypoglycemic Agents; 0/Peptides; 0/Venoms; 106388-42-5/Peptide YY; 123583-37-9/peptide YY (3-36); 141732-76-5/exenatide

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