Effects of different intermittent peptide YY (3-36) dosing strategies on food intake, body weight, and adiposity in diet-induced obese rats.

Abstract

Chronic administration of anorexigenic substances to experimental animals by injections or continuous infusion typically produces either no effect or a transient reduction in food intake and body weight. Our aim here was to identify an intermittent dosing strategy for intraperitoneal infusion of peptide YY(3-36) [PYY(3-36)] that produces a sustained reduction in daily food intake and adiposity in diet-induced obese rats. Rats (665+/-10 g body wt, 166+/-7 g body fat) with intraperitoneal catheters tethered to infusion swivels had free access to a high-fat diet. Vehicle-treated rats (n=23) had relatively stable food intake, body weight, and adiposity during the 9-wk test period. None of 15 PYY(3-36) dosing regimens administered in succession to a second group of rats (n=22) produced a sustained 15-25% reduction in daily food intake for >5 days, although body weight and adiposity were reduced across the 9-wk period by 12% (594+/-15 vs. 672+/-15 g) and 43% (96+/-7 vs. 169+/-9 g), respectively. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was >or=3 h appeared to be due in part to an increase in food intake between infusions. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was <3 h suggested possible receptor downregulation and tolerance to frequent PYY(3-36) administration; however, food intake significantly increased when PYY(3-36) treatments were discontinued for 1 day following apparent loss in treatment efficacies. Together, these results demonstrate the development of a potent homeostatic response to increase food intake when PYY(3-36) reduces food intake and energy reserves in diet-induced obese rats.

• Authors: Roger D Reidelberger, Alvin C Haver, Prasanth K Chelikani, James L Buescher
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 295 Issue 2 Pg. R449-58 (Aug 2008) ISSN: 0363-6119 [Print] United States
• PMID: 18550871 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Appetite Depressants
• Dietary Fats
• Peptide Fragments
• Peptide YY
• peptide YY (3-36)

Topics

• Adiposity (drug effects)
• Animals
• Appetite Depressants (administration & dosage)
• Behavior, Animal (drug effects)
• Body Weight (drug effects)
• Dietary Fats
• Disease Models, Animal
• Drug Administration Schedule
• Eating (drug effects)
• Homeostasis
• Infusions, Parenteral
• Male
• Obesity (drug therapy, etiology, physiopathology)
• Peptide Fragments
• Peptide YY (administration & dosage)
• Rats
• Rats, Sprague-Dawley
• Time Factors