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Normal feeding behavior, body weight and leptin response require the neuropeptide Y Y2 receptor

Nature Medicine volume 5, pages 1188–1193 (1999)Cite this article

Abstract

Neuropeptide Y (NPY), a 36-amino-acid peptide widely expressed in the brain1 is involved in many physiological responses2, including hypothalamic control of food intake and cardiovascular homeostasis. NPY mediates its effects through binding to the Y1, Y2 and Y5 G-protein-coupled receptors3,4,5,6. Little is known of the role of the Y2 receptor in mediating the different NPY effects. We inactivated the Y2 receptor subtype in mice and found that these mice developed increased body weight, food intake and fat deposition. The null mutant mice showed an attenuated response to leptin administration but a normal response to NPY-induced food intake and intact regulation of re-feeding and body weight after starvation. An absence of the Y2 receptor subtype also affected the basal control of heart rate, but did not influence blood pressure. These findings indicate an inhibitory role for the Y2 receptor subtype in the central regulation of body weight and control of food intake.

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Figure 1: Y2 receptor disruption by homologous recombination.
Figure 2: The effect of normal-fat and high-fat diet on body weight and plasma composition.
Figure 3: Effects of starvation, NPY and leptin on food intake.

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Acknowledgements

We thank P. Mombaerts for the gift of the IRES/tau/lacZ plasmid. We thank M. Byström, M. Edlund, H. Fält, O. Karlsson, M. Lindberg and U. Marklund for input in the creation and characterization of the polyclonal antibodies, and L. Amrut Fors for determination of the plasma components. We thank J. Wagner and S. Nyström for comments on the manuscript. This research was supported by the Swedish Medical Research Council and Kapten Arthur Ericssons Foundation to P.E. P.N. was a fellow of the WennerGren Foundation and Karolinska Institute, and J.M.C. was a fellow of the European Molecular Biology Organization.

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Author notes

  1. Josep M. Canals

    Present address: Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, IDIBAPS, Casanova 143, 08036, Barcelona, Spain

  2. Hessameh Hassani and Josep M. Canals: H.H. and J.M.C. contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Biochemistry and Biophysics, Laboratory of Molecular Neurobiology, Karolinska Institute, Stockholm, S17177 , Sweden

    Philippe Naveilhan, Hessameh Hassani, Josep M. Canals, Ernest Arenas & Patrik Ernfors

  2. Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, S17177, Sweden

    Peter Thoren

  3. Department of Molecular Biology, Astra Hässle AB, Tvistevägen 48, Umeå, S-907 36, Sweden

    A. Jonas Ekstrand & Åsa Larefalk

  4. Department Cell Biology & Biochemistry, Astra Hässle AB, S-431, Mölndal, 83, Sweden

    Vijay Chhajlani, Karin Gedda & Lennart Svensson

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Correspondence to Philippe Naveilhan or Patrik Ernfors.

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Naveilhan, P., Hassani, H., Canals, J. et al. Normal feeding behavior, body weight and leptin response require the neuropeptide Y Y2 receptor. Nat Med 5, 1188–1193 (1999). https://doi.org/10.1038/13514

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