Chelikani PK, Haver AC, Reidelberger RD. Intermittent intraperitoneal infusion of peptide YY(3-36) reduces daily food intake and adiposity in obese rats. Am J Physiol Regul Integr Comp Physiol 293: R39-R46, 2007. First published April 11, 2007; doi:10.1152/ajpregu.00164.2007 ] 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 Ͼ25%) received twice daily intraperitoneal infusion of vehicle (n ϭ 18) or PYY(3-36) (n ϭ 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 ⅐ kg Ϫ1 ⅐ min Ϫ1 was reduced to 10 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 on day 10 and then increased to 17 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 on day 13. This dosing strategy produced a sustained reduction in daily caloric intake of 11-32% and prevented body weight gain (8 Ϯ 6 vs. 51 Ϯ 11 g) and fat deposition (4.4 Ϯ 7.6 vs. 41.0 Ϯ 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.peptide; anorexia; body weight; body fat PEPTIDE YY (PYY), neuropeptide Y, and pancreatic polypeptide comprise a family of structurally related gut-brain peptides with diverse actions mediated by five known receptors (12). Endocrine cells of the distal gut provide a major source of PYY. Food intake releases at least two major forms of PYY into the circulation: PYY(1-36) and PYY(3-36); other predicted or detected isoforms include Ser 13 -phosphorylated PYY(1-36) and PYY(3-36), glycine-extended carboxyl termini of both the phosphorylated and nonphosphorylated forms, and [Pro 34 ]PYY(3-36) (4,17,21,24). Systemic administration of PYY(3-36) potently inhibits food intake in rodents, monkeys, and humans (11,15,19,27,28,33,40), whereas PYY(1-36) appears to be significantly less potent in rats (15) and humans (39). Targeted deletion of the PYY gene produces an obese phenotype in mice (13). Obese humans appear to have a blunted plasma PYY response to food intake (10, 28); however, PYY(3-36) appears to decrease food intake similarly in lean and obese humans (10, 39). These results suggest that PYY(3-36) may act physiologically to reduce food intake and body adiposity and that insufficient produc...