title: Atherogenic diets exacerbate colitis in mice deficient in glutathione peroxidase.
abstract: 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.
authors.affiliation: Department of Radiation Biology, Beckman Research Institute of City of Hope, Duarte, California, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.forename: R Steven
authors.initials: RS
authors.lastname: Esworthy
authors.forename: Byung-Wook
authors.initials: BW
authors.lastname: Kim
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Synold
authors.forename: David D
authors.initials: DD
authors.lastname: Smith
authors.forename: Fong-Fong
authors.initials: FF
authors.lastname: Chu
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology*; D015153:Blotting, Western; D002784:Cholesterol / Q000378:metabolism; D003092:Colitis / Q000209:etiology* / Q000473:pathology; D003424:Crohn Disease / Q000209:etiology / Q000473:pathology; D003840:Deoxycholic Acid / Q000378:metabolism; D004036:Diet, Atherogenic; D000091342:Endoplasmic Reticulum Chaperone BiP; D005234:Fatty Liver / Q000209:etiology / Q000473:pathology; D005243:Feces / Q000737:chemistry; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005979:Glutathione Peroxidase / Q000502:physiology*; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003840:Deoxycholic Acid; D002784:Cholesterol; C492172:Gpx2 protein, mouse; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse