IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51077-3.html
   My bibliography  Save this article

A homeostatic gut-to-brain insulin antagonist restrains neuronally stimulated fat loss

Author

Listed:
  • Chung-Chih Liu

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Ayub Khan

    (The Scripps Research Institute)

  • Nicolas Seban

    (The Scripps Research Institute)

  • Nicole Littlejohn

    (The Scripps Research Institute)

  • Aayushi Shah

    (The Scripps Research Institute)

  • Supriya Srinivasan

    (The Scripps Research Institute)

Abstract

In C. elegans mechanisms by which peripheral organs relay internal state information to the nervous system remain unknown, although strong evidence suggests that such signals do exist. Here we report the discovery of a peptide of the ancestral insulin superfamily called INS-7 that functions as an enteroendocrine peptide and is secreted from specialized cells of the intestine. INS-7 secretion is stimulated by food withdrawal, increases during fasting and acts as a bona fide gut-to-brain peptide that attenuates the release of a neuropeptide that drives fat loss in the periphery. Thus, INS-7 functions as a homeostatic signal from the intestine that gates the neuronal drive to stimulate fat loss during food shortage. Mechanistically, INS-7 functions as an antagonist at the canonical DAF-2 receptor and functions via FOXO and AMPK signaling in ASI neurons. Phylogenetic analysis suggests that INS-7 bears greater resemblance to members of the broad insulin/relaxin superfamily than to conventional mammalian insulin and IGF peptides. The discovery of an endogenous insulin antagonist secreted by specialized intestinal cells with enteroendocrine functions suggests unexpected and important properties of the intestine and its role in directing neuronal functions.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51077-3
    DOI: 10.1038/s41467-024-51077-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51077-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-51077-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. Rachel L. Batterham & Michael A. Cowley & Caroline J. Small & Herbert Herzog & Mark A. Cohen & Catherine L. Dakin & Alison M. Wren & Audrey E. Brynes & Malcolm J. Low & Mohammad A. Ghatei & Roger D. C, 2002. "Gut hormone PYY3-36 physiologically inhibits food intake," Nature, Nature, vol. 418(6898), pages 650-654, August.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Junjun Gao & Song Zhang & Pan Deng & Zhigang Wu & Bruno Lemaitre & Zongzhao Zhai & Zheng Guo, 2024. "Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    2. Abbe M. Mhd Jalil & Emilie Combet & Christine A. Edwards & Ada L. Garcia, 2019. "Effect of β-Glucan and Black Tea in a Functional Bread on Short Chain Fatty Acid Production by the Gut Microbiota in a Gut Digestion/Fermentation Model," IJERPH, MDPI, vol. 16(2), pages 1-14, January.
    3. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51077-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.