High fat diets induce colonic epithelial cell stress and inflammation that is reversed by IL-22

Gulhane, Max, Murray, Lydia, Lourie, Rohan, Tong, Hui, Sheng, Yong H., Wang, Ran, Kang, Alicia, Schreiber, Veronika, Wong, Kuan Yau, Magor, Graham, Denman, Stuart, Begun, Jakob, Florin, Timothy H., Perkins, Andrew, Cuiv, Paraic O., McGuckin, Michael A. and Hasnain, Sumaira Z. (2016) High fat diets induce colonic epithelial cell stress and inflammation that is reversed by IL-22. Scientific Reports, 6 . doi:10.1038/srep28990

Author Gulhane, Max
Murray, Lydia
Lourie, Rohan
Tong, Hui
Sheng, Yong H.
Wang, Ran
Kang, Alicia
Schreiber, Veronika
Wong, Kuan Yau
Magor, Graham
Denman, Stuart
Begun, Jakob
Florin, Timothy H.
Perkins, Andrew
Cuiv, Paraic O.
McGuckin, Michael A.
Hasnain, Sumaira Z.
Title High fat diets induce colonic epithelial cell stress and inflammation that is reversed by IL-22
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2016-06-28
Year available 2016
Sub-type Article (original research)
DOI 10.1038/srep28990
Open Access Status DOI
Volume 6
Total pages 17
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Formatted abstract
Prolonged high fat diets (HFD) induce low-grade chronic intestinal inflammation in mice, and diets high in saturated fat are a risk factor for the development of human inflammatory bowel diseases. We hypothesized that HFD-induced endoplasmic reticulum (ER)/oxidative stress occur in intestinal secretory goblet cells, triggering inflammatory signaling and reducing synthesis/secretion of proteins that form the protective mucus barrier. In cultured intestinal cells non-esterified long-chain saturated fatty acids directly increased oxidative/ER stress leading to protein misfolding. A prolonged HFD elevated the intestinal inflammatory cytokine signature, alongside compromised mucosal barrier integrity with a decrease in goblet cell differentiation and Muc2, a loss in the tight junction protein, claudin-1 and increased serum endotoxin levels. In Winnie mice, that develop spontaneous colitis, HFD-feeding increased ER stress, further compromised the mucosal barrier and increased the severity of colitis. In obese mice IL-22 reduced ER/oxidative stress and improved the integrity of the mucosal barrier, and reversed microbial changes associated with obesity with an increase in Akkermansia muciniphila. Consistent with epidemiological studies, our experiments suggest that HFDs are likely to impair intestinal barrier function, particularly in early life, which partially involves direct effects of free-fatty acids on intestinal cells, and this can be reversed by IL-22 therapy.
Keyword Endoplasmic reticulum (ER)
High fat diets (HFD)
Low-grade chronic intestinal inflammation
Akkermansia muciniphila
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
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