High fat diet induces microbiota-dependent silencing of enteroendocrine cells
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 t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/48479 |
| _version_ | 1811201393886756864 |
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| author | Lihua Ye Olaf Mueller Jennifer Bagwell Michel Bagnat Rodger A Liddle John F Rawls |
| author_facet | Lihua Ye Olaf Mueller Jennifer Bagwell Michel Bagnat Rodger A Liddle John F Rawls |
| author_sort | Lihua Ye |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:20:00Z |
| format | Article |
| id | doaj.art-77c100c778dd4570a0002b83b2ede619 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:20:00Z |
| publishDate | 2019-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-77c100c778dd4570a0002b83b2ede6192022-12-22T03:52:08ZengeLife Sciences Publications LtdeLife2050-084X2019-12-01810.7554/eLife.48479High fat diet induces microbiota-dependent silencing of enteroendocrine cellsLihua Ye0https://orcid.org/0000-0001-6790-9743Olaf Mueller1Jennifer Bagwell2Michel Bagnat3https://orcid.org/0000-0002-3829-0168Rodger A Liddle4John F Rawls5https://orcid.org/0000-0002-5976-5206Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States; Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, United StatesDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United StatesDepartment of Cell Biology, Duke University School of Medicine, Durham, United StatesDepartment of Cell Biology, Duke University School of Medicine, Durham, United StatesDivision of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, United StatesDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States; Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, United StatesEnteroendocrine 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.https://elifesciences.org/articles/48479enteroendocrine cellsmicrobiomeDanio reriozebrafishAcinetobacterdigestive physiology |
| spellingShingle | Lihua Ye Olaf Mueller Jennifer Bagwell Michel Bagnat Rodger A Liddle John F Rawls High fat diet induces microbiota-dependent silencing of enteroendocrine cells eLife enteroendocrine cells microbiome Danio rerio zebrafish Acinetobacter digestive physiology |
| title | High fat diet induces microbiota-dependent silencing of enteroendocrine cells |
| title_full | High fat diet induces microbiota-dependent silencing of enteroendocrine cells |
| title_fullStr | High fat diet induces microbiota-dependent silencing of enteroendocrine cells |
| title_full_unstemmed | High fat diet induces microbiota-dependent silencing of enteroendocrine cells |
| title_short | High fat diet induces microbiota-dependent silencing of enteroendocrine cells |
| title_sort | high fat diet induces microbiota dependent silencing of enteroendocrine cells |
| topic | enteroendocrine cells microbiome Danio rerio zebrafish Acinetobacter digestive physiology |
| url | https://elifesciences.org/articles/48479 |
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