Endocrine Abstracts

Peptide YY(3-36) (PYY(3-36)) is secreted from endocrine L-cells of the gastrointestinal tract and is thought to induce post-prandial satiety by inhibiting the release of neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus via the hypothalamic neuropeptide Y2 receptor (Y2R). NPY mRNA expression in the hypothalamus is markedly increased with fasting. Therefore, we investigated the effect of intraperitoneal (i.p.) injections of PYY(3-36) (120ug/kg) on food intake versus saline controls in mice fasted for 0, 6, 12, 18, 24 and 30 hours. We show that peripheral PYY(3-36) injections produce a significant reduction in food intake regardless of the duration of fasting. However, the longer the fast time the sooner the effects of PYY(3-36) are seen [PYY(3-36) versus saline - 6hr fast food intake 0-1hr p=ns, 1-2hr p<0.05; 24hr fast food intake 0-1hr p<0.05, 1-2hr p<0.05]. PYY 3-36 also inhibited food intake [2-4hr p<0.05] in fed mice. We also show evidence of a possible over-swing effect of i.p. PYY(3-36) injections which produce a significant reciprocal increase in food intake. Together these data indicate the anorexigenic actions of PYY3-36 are not dependent on fasting induced increase in hypothalamic NPY levels.