PUBLICATION
High fat diet induces microbiota-dependent silencing of enteroendocrine cells
- Authors
- Ye, L., Mueller, O., Bagwell, J., Bagnat, M., Liddle, R.A., Rawls, J.F.
- ID
- ZDB-PUB-191204-25
- Date
- 2019
- Source
- eLIFE 8: (Journal)
- Registered Authors
- Bagnat, Michel, Rawls, John F., Ye, Lihua
- Keywords
- developmental biology, infectious disease, microbiology, zebrafish
- MeSH Terms
-
- Acinetobacter/physiology
- Adaptation, Physiological/physiology
- Animals
- Diet, High-Fat*
- Dietary Fats/administration & dosage
- Endoplasmic Reticulum Stress/physiology
- Enteroendocrine Cells/drug effects
- Enteroendocrine Cells/physiology*
- Gastrointestinal Microbiome/drug effects
- Gastrointestinal Microbiome/physiology*
- Germ-Free Life
- Intestinal Mucosa/drug effects
- Intestinal Mucosa/microbiology
- Intestinal Mucosa/physiology*
- Signal Transduction/physiology
- Zebrafish/microbiology
- Zebrafish/physiology*
- PubMed
- 31793875 Full text @ Elife
Citation
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:.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping