PYY(3-36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity.
The gut hormone peptide YY (PYY) was recently proposed to comprise an endogenous satiety factor. We have studied acute anorectic functions of PYY(3-36) in mice and rats, as well as metabolic effects of chronic PYY(3-36) administration to diet-induced obese (DIO) mice and rats. A single intraperitoneal injection of PYY(3-36) inhibited food intake in mice, but not in rats. We next investigated the effects of increasing doses (100, 300, and 1,000 microg.kg-1.day-1) of PYY(3-36) administered subcutaneously via osmotic minipumps on food intake and body weight in DIO C57BL/6J mice. Whereas only the highest dose (1,000 microg.kg-1.day-1) of PYY(3-36) significantly reduced food intake over the first 3 days, body weight gain was dose dependently reduced, and on day 28 the group treated with 1,000 microg.kg-1.day-1 PYY(3-36) weighed approximately 10% less than the vehicle-treated group. Mesenteric, epididymal, retroperitoneal, and inguinal fat pad weight was dose dependently reduced. Subcutaneous administration of PYY(3-36) (250 and 1,000 microg.kg-1.day-1) for 28 days reduced body weight and improved glycemic control in glucose-intolerant DIO rats. Neither 250 nor 1,000 microg/kg PYY(3-36) elicited a conditioned taste aversion in male rats.
Vrang
Niels
N
Rheoscience, Glerupvej 2, 2610 Rødovre, Denmark. nv@rheoscience.com
Madsen
Andreas Nygaard
AN
Tang-Christensen
Mads
M
Hansen
Gitte
G
Larsen
Philip Just
PJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology; D010446:Peptide Fragments; D019894:Peptide YY / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012377:Rodentia; D013649:Taste / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36)