Access

Letters to Nature

Nature 418, 650-654 (8 August 2002) | doi:10.1038/nature00887; Received 9 January 2002; Accepted 13 May 2002

There is a Brief Communications Arising (8 July 2004) associated with this document.

Open Innovation Challenges

Gut hormone PYY3-36 physiologically inhibits food intake

Rachel L. Batterham1,2, Michael A. Cowley2,3,4, Caroline J. Small1, Herbert Herzog5, Mark A. Cohen1, Catherine L. Dakin1, Alison M. Wren1, Audrey E. Brynes1, Malcolm J. Low4, Mohammad A. Ghatei1, Roger D. Cone4 & Stephen R. Bloom1

  1. Imperial College Faculty of Medicine at Hammersmith Campus, Du Cane Road, London W12 0NN, UK
  2. Oregon National Primate Research Centre, Oregon Health and Sciences University, 505 NW 185th, Beaverton, Oregon 97006, USA
  3. The Vollum Institute, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201, USA
  4. Neurobiology Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia
  5. These authors contributed equally to this work

Correspondence to: Stephen R. Bloom1 Correspondence and requests for materials should be addressed to S.R.B. (e-mail: Email: s.bloom@ic.ac.uk).

Top

Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus1. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons2 in the arcuate nucleus, which is accessible to peripheral hormones3. Peptide YY3-36 (PYY3-36), a Y2R agonist4, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal5, 6, 7. Here we show that peripheral injection of PYY3-36 in rats inhibits food intake and reduces weight gain. PYY3-36 also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY3-36 increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY3-36 inhibits food intake. PYY3-36 also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons8. In humans, infusion of normal postprandial concentrations of PYY3-36 significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut–hypothalamic pathway.

  1. Imperial College Faculty of Medicine at Hammersmith Campus, Du Cane Road, London W12 0NN, UK
  2. Oregon National Primate Research Centre, Oregon Health and Sciences University, 505 NW 185th, Beaverton, Oregon 97006, USA
  3. The Vollum Institute, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201, USA
  4. Neurobiology Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia
  5. These authors contributed equally to this work

Correspondence to: Stephen R. Bloom1 Correspondence and requests for materials should be addressed to S.R.B. (e-mail: Email: s.bloom@ic.ac.uk).