Format

Send to

Choose Destination
Inflamm Bowel Dis. 2010 Dec;16(12):2043-54. doi: 10.1002/ibd.21317.

Atherogenic diets exacerbate colitis in mice deficient in glutathione peroxidase.

Author information

1
Department of Radiation Biology, Beckman Research Institute of City of Hope, Duarte, California, USA.

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.

PMID:
20848490
PMCID:
PMC2991606
DOI:
10.1002/ibd.21317
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center