Effects of different intermittent peptide YY (3-36) dosing strategies on food intake, body weight, and adiposity in diet-induced obese rats.
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.
Department of Veterans Affairs, Nebraska Western Iowa Health Care System, Omaha, NE 68105, USA. roger.reidelberger@va.gov
Roger D
RD
Reidelberger
Alvin C
AC
Haver
Prasanth K
PK
Chelikani
James L
JL
Buescher
D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D004041:Dietary Fats; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects*; D006706:Homeostasis; D007263:Infusions, Parenteral; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010446:Peptide Fragments; D019894:Peptide YY / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001067:Appetite Depressants; D004041:Dietary Fats; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36)