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High fat diet induces microbiota-dependent silencing of enteroendocrine cells.

Publication ,  Journal Article
Ye, L; Mueller, O; Bagwell, J; Bagnat, M; Liddle, RA; Rawls, JF
Published in: Elife
December 3, 2019

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 bacteria, 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.

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Published In

Elife

DOI

EISSN

2050-084X

Publication Date

December 3, 2019

Volume

8

Location

England

Related Subject Headings

  • Zebrafish
  • Signal Transduction
  • Intestinal Mucosa
  • Germ-Free Life
  • Gastrointestinal Microbiome
  • Enteroendocrine Cells
  • Endoplasmic Reticulum Stress
  • Dietary Fats
  • Diet, High-Fat
  • Animals
 

Citation

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ICMJE
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Ye, L., Mueller, O., Bagwell, J., Bagnat, M., Liddle, R. A., & Rawls, J. F. (2019). High fat diet induces microbiota-dependent silencing of enteroendocrine cells. Elife, 8. https://doi.org/10.7554/eLife.48479
Ye, Lihua, Olaf Mueller, Jennifer Bagwell, Michel Bagnat, Rodger A. Liddle, and John F. Rawls. “High fat diet induces microbiota-dependent silencing of enteroendocrine cells.Elife 8 (December 3, 2019). https://doi.org/10.7554/eLife.48479.
Ye L, Mueller O, Bagwell J, Bagnat M, Liddle RA, Rawls JF. High fat diet induces microbiota-dependent silencing of enteroendocrine cells. Elife. 2019 Dec 3;8.
Ye, Lihua, et al. “High fat diet induces microbiota-dependent silencing of enteroendocrine cells.Elife, vol. 8, Dec. 2019. Pubmed, doi:10.7554/eLife.48479.
Ye L, Mueller O, Bagwell J, Bagnat M, Liddle RA, Rawls JF. High fat diet induces microbiota-dependent silencing of enteroendocrine cells. Elife. 2019 Dec 3;8.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

December 3, 2019

Volume

8

Location

England

Related Subject Headings

  • Zebrafish
  • Signal Transduction
  • Intestinal Mucosa
  • Germ-Free Life
  • Gastrointestinal Microbiome
  • Enteroendocrine Cells
  • Endoplasmic Reticulum Stress
  • Dietary Fats
  • Diet, High-Fat
  • Animals