Intermittent intraperitoneal infusion of peptide YY(3-36) reduces daily food intake and adiposity in obese rats.
Peptide YY(3-36) [PYY(3-36)] is a gut-brain peptide that decreases food intake when administered by intravenous infusion to lean and obese humans and rats. However, chronic administration of PYY(3-36) by osmotic minipump to lean and obese rodents produces only a transient reduction in daily food intake and weight gain. It has recently been shown that 1-h intravenous infusions of PYY(3-36) every other hour for 10 days produced a sustained reduction in daily food intake, body weight, and adiposity in lean rats. Here, we determined whether intermittent delivery of PYY(3-36) can produce a similar response in diet-induced obese rats. During a 21-day period, obese rats (body fat >25%) received twice daily intraperitoneal infusion of vehicle (n = 18) or PYY(3-36) (n = 24) during hours 1-3 and 7-9 of the dark period. Rats had free access to both a 45% fat solid diet and a 29% fat liquid diet; intakes were determined from continuous computer recording of changes in food container weights. To sustain a 15-25% reduction in daily caloric intake, the initial PYY(3-36) dose of 30 pmol.kg(-1).min(-1) was reduced to 10 pmol.kg(-1).min(-1) on day 10 and then increased to 17 pmol.kg(-1).min(-1) on day 13. This dosing strategy produced a sustained reduction in daily caloric intake of 11-32% and prevented body weight gain (8 +/- 6 vs. 51 +/- 11 g) and fat deposition (4.4 +/- 7.6 vs. 41.0 +/- 12.8 g). These results indicate that intermittent intraperitoneal infusion of PYY(3-36) can produce a sustained reduction in food intake and adiposity in diet-induced obese rodents consuming palatable high-fat foods.
Chelikani
Prasanth K
PK
Department of Veterans Affairs-Nebraska Western Iowa Health Care System, Research Service (151), 4101 Woolworth Ave., Omaha, NE 68105, USA.
Haver
Alvin C
AC
Reidelberger
Roger D
RD
D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology; D010446:Peptide Fragments; D019894:Peptide YY / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36)