| First Author | Gao Q | Year | 2010 |
| Journal | Inflamm Bowel Dis | Volume | 16 |
| Issue | 12 | Pages | 2043-54 |
| PubMed ID | 20848490 | Mgi Jnum | J:329373 |
| Mgi Id | MGI:7344149 | Doi | 10.1002/ibd.21317 |
| Citation | Gao Q, et al. (2010) Atherogenic diets exacerbate colitis in mice deficient in glutathione peroxidase. Inflamm Bowel Dis 16(12):2043-54 |
| abstractText | 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-alpha 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. |
