High fat diet induces microbiota-dependent silencing of enteroendocrine cells
- Duke University School of Medicine, United States
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.
Data availability
Sequencing data have been deposited at SRA under Bioproject accession number PRJNA532723.All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1-8, Supplemental Figure 3. The link for access the source data: https://dx.doi.org/10.5061/dryad.mb004d1
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Data from: High fat diet induces microbiota-dependent silencing of enteroendocrine cellsDryad Digital Repository, doi:10.5061/dryad.j1fd7.
Article and author information
Author details
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.
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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High fat diet induces microbiota-dependent silencing of enteroendocrine cells
eLife 8:e48479.
https://doi.org/10.7554/eLife.48479
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