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.
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: Anne Figge; Frank Lammert; Beverly Paigen; Anne Henkel; Siegfried Matern; Ron Korstanje; Benjamin L Shneider; Frank Chen; Erik Stoltenberg; Kathryn Spatz; Farzana Hoda; David E Cohen; Richard M Green Journal: J Biol Chem Date: 2003-10-21 Impact factor: 5.157
Authors: Hong Li; Christopher Lelliott; Pernilla Håkansson; Karolina Ploj; Anna Tuneld; Martina Verolin-Johansson; Lambertus Benthem; Björn Carlsson; Leonard Storlien; Erik Michaëlsson Journal: Metabolism Date: 2008-12 Impact factor: 8.694
Authors: Lynnette R Ferguson; Andrew N Shelling; Brian L Browning; Claudia Huebner; Ivonne Petermann Journal: Mutat Res Date: 2007-06-02 Impact factor: 2.433
Authors: Reema Goel; Brian Boylan; Lynn Gruman; Peter J Newman; Paula E North; Debra K Newman Journal: Am J Physiol Gastrointest Liver Physiol Date: 2007-10-11 Impact factor: 4.052
Authors: Byung-Wook Kim; R Steven Esworthy; Maria A Hahn; Gerd P Pfeifer; Fong-Fong Chu Journal: Free Radic Biol Med Date: 2012-02-15 Impact factor: 7.376