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Agouti-related peptide–expressing neurons are mandatory for feeding

Nature Neuroscience volume 8, pages 1289–1291 (2005)Cite this article

Abstract

Multiple hormones controlling energy homeostasis regulate the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Nevertheless, inactivation of the genes encoding NPY and/or AgRP has no impact on food intake in mice. Here we demonstrate that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis.

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Figure 1: Ablation of AgRP and POMC neurons.
Figure 2: Ablation of AgRP neurons causes acute anorexia, whereas ablation of POMC neurons leads to hyperphagia and obesity.

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Acknowledgements

We wish to thank S. Irlenbusch for expert technical support and G. Schmall for excellent secretarial assistance. We wish to thank F. Schwenk and J. Seibler (Artemis Pharmaceuticals) for providing Rosa26-β-Gal-mice. This work was supported by grants from the Zentrum für Molekulare Medizin der Universität zu Köln (TV-2) and the European Union (LSHM-CT-2003-503041) to J.C.B., from the Köln Fortune Program (to L.P.), from the US National Institutes of Health (DK-07386 and DK-060711 to T.L.H. and DK68384 to G.S.B), and from the Deutsche Forschungsgemeinschaft (BU1410/1-1 to T.B.).

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Authors and Affiliations

  1. Department of Mouse Genetics and Metabolism, Institute for Genetics and Center for Molecular Medicine (CMMC), University of Cologne, Zülpicher Str. 47, Köln, 50674, Germany

    Eva Gropp, Ruth Janoschek, Leona Plum, Brigitte Hampel & Jens C Brüning

  2. Department of Obstetrics, Department of Neurobiology and Section of Comparative Medicine, Gynecology & Reproductive Sciences, Yale University School of Medicine, 333 Cedar St. FMB 339, New Haven, 06520, Connecticut, USA

    Marya Shanabrough, Erzsebet Borok & Tamas L Horvath

  3. Department of Genetics and Pediatrics, Stanford University School of Medicine, 279 Campus Drive, Stanford, 94305, California, USA

    Allison W Xu & Gregory S Barsh

  4. Cellular Immunology, Institute for Genetics, University of Cologne, Zülpicher Str. 47, Köln, 50674, Germany

    Thorsten Buch

  5. Second Department of Internal Medicine, University of Cologne, Kerpener Str. 62, Köln, 50924, Germany

    Leona Plum

  6. Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Ave., Boston, 02215, Massachusetts, USA

    Nina Balthasar

  7. Unit for Pathophysiology, I. Medizinische Klinik und Poliklinik, Johannes-Gutenberg-University Mainz, Obere Zahlbacher Str. 63, Mainz, 55131, Germany

    Ari Waisman

Authors
  1. Eva Gropp
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  2. Marya Shanabrough
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  7. Leona Plum
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  8. Nina Balthasar
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  9. Brigitte Hampel
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  10. Ari Waisman
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  11. Gregory S Barsh
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  12. Tamas L Horvath
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Corresponding authors

Correspondence to Tamas L Horvath or Jens C Brüning.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Breeding strategies. (PDF 416 kb)

Supplementary Fig. 2

Specificity of AgRP cell ablation. (PDF 220 kb)

Supplementary Fig. 3

Unaltered plasma corticosterone concentrations in AgRPDTR mice versus hypocortisolism in POMCDTR mice. (PDF 244 kb)

Supplementary Methods (PDF 42 kb)

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Gropp, E., Shanabrough, M., Borok, E. et al. Agouti-related peptide–expressing neurons are mandatory for feeding. Nat Neurosci 8, 1289–1291 (2005). https://doi.org/10.1038/nn1548

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