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Gut hormone PYY(3-36) physiologically inhibits food intake


Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY(3-36) (PYY(3-36)), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY(3-36) in rats inhibits food intake and reduces weight gain. PYY(3-36) also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY(3-36) increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY(3-36) inhibits food intake. PYY(3-36) also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY(3-36) significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY(3-36) may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway.

Type Journal
ISBN 0028-0836 (Print)
Authors Batterham, R. L.;Cowley, M. A.;Small, C. J.;Herzog, H.;Cohen, M. A.;Dakin, C. L.;Wren, A. M.;Brynes, A. E.;Low, M. J.;Ghatei, M. A.;Cone, R. D.;Bloom, S. R. :
Garvan Authors Prof Herbert Herzog
Publisher Name NATURE
Published Date 2002-01-01 00:00:00
Published Volume 418
Published Issue 6898
Published Pages 650-4
Status Published In-print