Effects of glycine-extended and serine13-phosphorylated forms of peptide YY on food intake in rats

The gut hormone peptide YY(3-36)-amide [PYY(3-36)-NH2] is significantly more potent than PYY(1-36)-NH2 in reducing food intake in rats and humans. Other Gly-extended and Ser(13)-phosphorylated PYY forms have been detected or predicted based upon known cellular processes of PYY synthesis and modification. Here we compared the effects of 3-h IV infusion of PYY(1-36)-NH2, PYY(3-36)-NH2, PYY(1-36)-Gly-OH, PYY(3-36)-Gly-OH, Ser(13)( PO3)-PYY(1-36)-NH2, Ser(13)(PO3)-PYY(3-36)-NH2, Ser13(PO3)-PYY(1-36)-Gly-OH, and Ser13(PO3)-PYY(3-36)-Gly-OH during the early dark period on food intake in freely feeding rats. PYY(3-36)-NH2 and Ser(13)(PO3)-PYY(3-36)-NH2 reduced food intake similarly at 50 pmol/kg/min, while only PYY(3-36)-NH2 reduced food intake at 15 pmol/kg/min. PYY(1-36)-NH2 and Ser(13)(PO3)PYY(1-36)-NH2 reduced food intake similarly at 50 and 150 pmol/kg/min. In contrast, PYY(1-36)-Gly-OH, PYY(3-36)-Gly-OH, Ser(13)(PO3)-PYY(3-36)-Gly-OH, and Ser(13)(PO3)-PYY(1-36)-Gly-OH had no effect on food intake at doses of 50 or 150 pmol/kg/min. Taken together, these results indicate that (i) PYY(3-36)-NH2 is significantly more potent than PYY(1-36)-NH2 in reducing food intake, (ii) Gly-extended forms of PYY are significantly less potent than non-extended forms, and (iii) Ser(13)-phosphorylation of PYY(3-36)-NH2 decreases the anorexigenic potency PYY(3-36)-NH2, but not PYY(1-36)-NH2. Thus, PYY(3-36)-NH2 appears to be the most potent PYY form for reducing food intake in rats. Published by Elsevier Inc.