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A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism

Author

Listed:
  • Lavinia Palamiuc

    (Department of Chemical Physiology and The Dorris Neuroscience Center
    The Scripps Research Institute)

  • Tallie Noble

    (Mira Costa College)

  • Emily Witham

    (The Scripps Research Institute)

  • Harkaranveer Ratanpal

    (The Scripps Research Institute)

  • Megan Vaughan

    (The Scripps Research Institute
    Kellogg School of Science and Technology, The Scripps Research Institute)

  • Supriya Srinivasan

    (Department of Chemical Physiology and The Dorris Neuroscience Center
    The Scripps Research Institute)

Abstract

Serotonin, a central neuromodulator with ancient ties to feeding and metabolism, is a major driver of body fat loss. However, mechanisms by which central serotonin action leads to fat loss remain unknown. Here, we report that the FLP-7 neuropeptide and its cognate receptor, NPR-22, function as the ligand-receptor pair that defines the neuroendocrine axis of serotonergic body fat loss in Caenorhabditis elegans. FLP-7 is secreted as a neuroendocrine peptide in proportion to fluctuations in neural serotonin circuit functions, and its release is regulated from secretory neurons via the nutrient sensor AMPK. FLP-7 acts via the NPR-22/Tachykinin2 receptor in the intestine and drives fat loss via the adipocyte triglyceride lipase ATGL-1. Importantly, this ligand-receptor pair does not alter other serotonin-dependent behaviours including food intake. For global modulators such as serotonin, the use of distinct neuroendocrine peptides for each output may be one means to achieve phenotypic selectivity.

Suggested Citation

  • Lavinia Palamiuc & Tallie Noble & Emily Witham & Harkaranveer Ratanpal & Megan Vaughan & Supriya Srinivasan, 2017. "A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14237
    DOI: 10.1038/ncomms14237
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    Cited by:

    1. Chung-Chih Liu & Ayub Khan & Nicolas Seban & Nicole Littlejohn & Aayushi Shah & Supriya Srinivasan, 2024. "A homeostatic gut-to-brain insulin antagonist restrains neuronally stimulated fat loss," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Tobias Clark & Vera Hapiak & Mitchell Oakes & Holly Mills & Richard Komuniecki, 2018. "Monoamines differentially modulate neuropeptide release from distinct sites within a single neuron pair," PLOS ONE, Public Library of Science, vol. 13(5), pages 1-22, May.

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