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. 2002 Aug 8;418(6898):650-4.
doi: 10.1038/nature00887.

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

Rachel L Batterham  1 , Michael A Cowley, Caroline J Small, Herbert Herzog, Mark A Cohen, Catherine L Dakin, Alison M Wren, Audrey E Brynes, Malcolm J Low, Mohammad A Ghatei, Roger D Cone, Stephen R Bloom
Affiliations

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

Rachel L Batterham et al. Nature. .

Abstract

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.

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Comment in

  • Obesity: keeping hunger at bay.
    Schwartz MW, Morton GJ. Schwartz MW, et al. Nature. 2002 Aug 8;418(6898):595-7. doi: 10.1038/418595a. Nature. 2002. PMID: 12167841 No abstract available.
  • Physiology: does gut hormone PYY3-36 decrease food intake in rodents?
    Tschöp M, Castañeda TR, Joost HG, Thöne-Reineke C, Ortmann S, Klaus S, Hagan MM, Chandler PC, Oswald KD, Benoit SC, Seeley RJ, Kinzig KP, Moran TH, Beck-sickinger AG, Koglin N, Rodgers RJ, Blundell JE, Ishii Y, Beattie AH, Holch P, Allison DB, Raun K, Madsen K, Wulff BS, Stidsen CE, Birringer M, Kreuzer OJ, Schindler M, Arndt K, Rudolf K, Mark M, Deng XY, Whitcomb DC, Halem H, Taylor J, Dong J, Datta R, Culler M, Craney S, Flora D, Smiley D, Heiman ML. Tschöp M, et al. Nature. 2004 Jul 8;430(6996):1 p following 165; discussion 2 p following 165. doi: 10.1038/nature02665. Nature. 2004. PMID: 15243972

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