Effects of glycine-extended and serine 13-phosphorylated forms of peptide YY on food intake in rats

Abstract

The gut hormone peptide YY(3-36)-amide [PYY(3-36)-NH 2] is significantly more potent than PYY(1-36)-NH 2 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)-NH 2, PYY(3-36)-NH 2, PYY(1-36)-Gly-OH, PYY(3-36)-Gly-OH, Ser 13(PO 3)-PYY(1-36)-NH 2, Ser 13(PO 3)-PYY(3-36)-NH 2, Ser 13(PO 3)-PYY(1-36)-Gly-OH, and Ser 13(PO 3)-PYY(3-36)-Gly-OH during the early dark period on food intake in freely feeding rats. PYY(3-36)-NH 2 and Ser 13(PO 3)-PYY(3-36)-NH 2 reduced food intake similarly at 50 pmol/kg/min, while only PYY(3-36)-NH 2 reduced food intake at 15 pmol/kg/min. PYY(1-36)-NH 2 and Ser 13(PO 3)-PYY(1-36)-NH 2 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(PO 3)-PYY(3-36)-Gly-OH, and Ser 13(PO 3)-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)-NH 2 is significantly more potent than PYY(1-36)-NH 2 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)-NH 2 decreases the anorexigenic potency PYY(3-36)-NH 2, but not PYY(1-36)-NH 2. Thus, PYY(3-36)-NH 2 appears to be the most potent PYY form for reducing food intake in rats.