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NPY mediates the rapid feeding and glucose metabolism regulatory functions of AgRP neurons

Author

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  • Linda Engström Ruud

    (Max Planck Institute for Metabolism Research
    University of Cologne
    University Hospital Cologne)

  • Mafalda M. A. Pereira

    (Max Planck Institute for Metabolism Research
    University of Cologne
    University Hospital Cologne)

  • Alain J. Solis

    (Max Planck Institute for Metabolism Research
    University of Cologne
    University Hospital Cologne)

  • Henning Fenselau

    (University of Cologne
    University Hospital Cologne
    Max Planck Institute for Metabolism Research)

  • Jens C. Brüning

    (Max Planck Institute for Metabolism Research
    University of Cologne
    University Hospital Cologne)

Abstract

Activation of Agouti-Related Peptide (AgRP)-expressing neurons promotes feeding and insulin resistance. Here, we examine the contribution of neuropeptide Y (NPY)-dependent signaling to the diverse physiological consequences of activating AgRP neurons. NPY-deficient mice fail to rapidly increase food intake during the first hour of either chemo- or optogenetic activation of AgRP neurons, while the delayed increase in feeding is comparable between control and NPY-deficient mice. Acutely stimulating AgRP neurons fails to induce systemic insulin resistance in NPY-deficient mice, while increased locomotor activity upon AgRP neuron stimulation in the absence of food remains unaffected in these animals. Selective re-expression of NPY in AgRP neurons attenuates the reduced feeding response and reverses the protection from insulin resistance upon optogenetic activation of AgRP neurons in NPY-deficient mice. Collectively, these experiments reveal a pivotal role of NPY-dependent signaling in mediating the rapid feeding inducing effect and the acute glucose regulatory function governed by AgRP neurons.

Suggested Citation

  • Linda Engström Ruud & Mafalda M. A. Pereira & Alain J. Solis & Henning Fenselau & Jens C. Brüning, 2020. "NPY mediates the rapid feeding and glucose metabolism regulatory functions of AgRP neurons," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14291-3
    DOI: 10.1038/s41467-020-14291-3
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    Cited by:

    1. Stephan Dodt & Noah V. Widdershooven & Marie-Luise Dreisow & Lisa Weiher & Lukas Steuernagel & F. Thomas Wunderlich & Jens C. Brüning & Henning Fenselau, 2024. "NPY-mediated synaptic plasticity in the extended amygdala prioritizes feeding during starvation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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