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Agouti-related peptide–expressing neurons are mandatory for feeding


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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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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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).

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