Dietary cholesterol directly induces acute inflammasome-dependent intestinal inflammation
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Supporting Information
Published version
Author(s)
Type
Journal Article
Abstract
Prolonged ingestion of a cholesterol- or saturated fatty acid-enriched diet induces chronic, often systemic, auto-inflammatory responses resulting in significant health problems worldwide. In vivo information regarding the local and direct inflammatory effect of these dietary components in the intestine and, in particular, on the intestinal epithelium is lacking. Here we report that both mice and zebrafish exposed to high-fat (HFDs) or high-cholesterol (HCDs) diets develop acute innate inflammatory responses within hours, reflected in the localized interleukin-1β-dependent accumulation of myeloid cells in the intestine. Acute HCD-induced intestinal inflammation is dependent on cholesterol uptake via Niemann-Pick C1-like 1 and inflammasome activation involving apoptosis-associated Speck-like protein containing a caspase recruitment domain, which leads to Caspase-1 activity in intestinal epithelial cells. Extended exposure to HCD results in localized, inflammation-dependent, functional dysregulation as well as systemic pathologies. Our model suggests that dietary cholesterol initiates intestinal inflammation in epithelial cells.
Date Issued
2014-12-01
Date Acceptance
2014-11-14
Citation
Nature Communications, 2014, 5, pp.1-14
ISSN
2041-1723
Publisher
Nature Research
Start Page
1
End Page
14
Journal / Book Title
Nature Communications
Volume
5
Copyright Statement
© 2014 Franze Progatzky et al. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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Sponsor
Wellcome Trust
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000347175700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
099859/Z/12/ZR
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
ZEBRAFISH
ACTIVATION
EXPRESSION
ACCUMULATION
PROMOTER
ABSORPTION
EPITHELIUM
PROTEIN
MODEL
Publication Status
Published
Article Number
ARTN 5864
Date Publish Online
2014-12-23