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  2. Microbiology and Infectious Disease
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High fat diet induces microbiota-dependent silencing of enteroendocrine cells

  1. Lihua Ye
  2. Olaf Mueller
  3. Jennifer Bagwell
  4. Michel Bagnat
  5. Rodger A Liddle  Is a corresponding author
  6. John F Rawls  Is a corresponding author
  1. Duke University School of Medicine, United States
Research Article
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Cite this article as: eLife 2019;8:e48479 doi: 10.7554/eLife.48479

Abstract

Enteroendocrine cells (EECs) are specialized sensory cells in the intestinal epithelium that sense and transduce nutrient information. Consumption of dietary fat contributes to metabolic disorders, but EEC adaptations to high fat feeding were unknown. Here, we established a new experimental system to directly investigate EEC activity in vivo using a zebrafish reporter of EEC calcium signaling. Our results reveal that high fat feeding alters EEC morphology and converts them into a nutrient insensitive state that is coupled to endoplasmic reticulum (ER) stress. We called this novel adaptation 'EEC silencing'. Gnotobiotic studies revealed that germ-free zebrafish are resistant to high fat diet induced EEC silencing. High fat feeding altered gut microbiota composition including enrichment of Acinetobacter species, and we identified an Acinetobacter strain sufficient to induce EEC silencing. These results establish a new mechanism by which dietary fat and gut microbiota modulate EEC nutrient sensing and signaling.

Article and author information

Author details

  1. Lihua Ye

    Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Olaf Mueller

    Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jennifer Bagwell

    Department of Cell Biology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michel Bagnat

    Department of Cell Biology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3829-0168
  5. Rodger A Liddle

    Department of Medicine, Duke University School of Medicine, Durham, United States
    For correspondence
    rodger.liddle@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
  6. John F Rawls

    Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States
    For correspondence
    john.rawls@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5976-5206

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK093399)

  • John F Rawls

National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK109368)

  • Rodger A Liddle

National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK081426)

  • John F Rawls

Pew Charitable Trusts

  • John F Rawls

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All zebrafish experiments conformed to the US Public Health Service Policy on Humane Care and Use of Laboratory Animals, using protocol number A115-16-05 approved by the Institutional Animal Care and Use Committee of Duke University.

Reviewing Editor

  1. Andrew J MacPherson, University of Bern, Switzerland

Publication history

  1. Received: May 15, 2019
  2. Accepted: November 26, 2019
  3. Accepted Manuscript published: December 3, 2019 (version 1)

Copyright

© 2019, Ye et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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