| Atherogenic diets exacerbate colitis in mice deficient in glutathione peroxidase. | |
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MedLine Citation:
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PMID: 20848490 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The proinflammatory effect of high-fat diet has been observed beyond the cardiovascular system, but there is little evidence to support its role in triggering inflammatory bowel disease. GPx1/2-double-knockout (DKO) mice deficient in 2 intracellular glutathione peroxidases, GPx1 and GPx2, on a C57BL/6 (B6) background, have mild ileocolitis on a conventional chow. METHODS: We fed B6 DKO mice 2 atherogenic diets to test the dietary effect on atherosclerosis and ileocolitis. Both atherogenic diets have high cholesterol-the Chol+/CA diet has cholic acid (CA), and the Chol+ diet has no CA. RESULTS: The Chol+/CA diet induced severe colitis, but not ileitis, in the DKO mice compared with the Chol+ and the Chol- control diet. On the Chol+/CA diet, the wild-type (WT) mice had levels of aortic lesions and hypercholesterolemia similar to those of DKO mice but had no intestinal pathology. The diet-associated inflammatory responses in the DKO mice included increased colonic proinflammatory serum amyloid A3 expression, plasma lipopolysaccharide, and TNF-α levels. The Chol+/CA diet lowered the expression of the unfolded protein response genes ATF6, CHOP, unspliced Xbp(U) , and Grp78/Bip, in WT and DKO mice compared with mice on the Chol- diet. CONCLUSIONS: We concluded that a cholesterol diet weakens the colon unfolded protein response, which can aggravate spontaneous colitis, leading to gut barrier breakdown. GPx has no impact on atherosclerosis without ultrahypercholesterolemia. |
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Authors:
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Qiang Gao; R Steven Esworthy; Byung-Wook Kim; Timothy W Synold; David D Smith; Fong-Fong Chu |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Inflammatory bowel diseases Volume: 16 ISSN: 1536-4844 ISO Abbreviation: Inflamm. Bowel Dis. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-24 Completed Date: 2011-03-31 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 9508162 Medline TA: Inflamm Bowel Dis Country: United States |
Other Details:
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Languages: eng Pagination: 2043-54 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Crohn's & Colitis Foundation of America, Inc. |
Affiliation:
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Department of Radiation Biology, Beckman Research Institute of City of Hope, Duarte, California, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atherosclerosis / etiology*, pathology* Blotting, Western Cholesterol / metabolism Colitis / etiology*, pathology Crohn Disease / etiology, pathology Deoxycholic Acid / metabolism Diet, Atherogenic* Fatty Liver / etiology, pathology Feces / chemistry Female Gas Chromatography-Mass Spectrometry Glutathione Peroxidase / physiology* Inflammation / etiology, pathology Inflammation Mediators / metabolism Lipopolysaccharides / metabolism Mice Mice, Inbred C57BL Mice, Knockout RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction Survival Rate Tumor Necrosis Factor-alpha / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA114569-05/CA/NCI NIH HHS; R01CA114569/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Inflammation Mediators; 0/Lipopolysaccharides; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; 57-88-5/Cholesterol; 83-44-3/Deoxycholic Acid; EC 1.11.1.-/Gpx2 protein, mouse; EC 1.11.1.-/glutathione peroxidase GPX1; EC 1.11.1.9/Glutathione Peroxidase |
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