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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Ye, L; Mueller, O; Bagwell, J; Bagnat, M; Liddle, RA; Rawls, JF

Published Date

  • December 3, 2019

Published In

Volume / Issue

  • 8 /

PubMed ID

  • 31793875

Pubmed Central ID

  • PMC6937151

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.48479

Language

  • eng

Conference Location

  • England