High-fat, high-cholesterol diet increases the incidence of gastritis in LDL receptor-negative mice.
Transgenic and knockout mice are widely used as models for atherogenesis studies. While developing a Helicobacter infection model in LDL receptor-negative (LDLR(-/-)) mice, we noticed that mice fed a high-fat, high-cholesterol diet often contracted gastritis independent of infection. To further investigate this finding, we studied 27 male and 18 female LDLR(-/-) mice fed high-fat, 1% or 1.25% cholesterol diets for 3 to 4 months. The extent of atherosclerosis was morphometrically analyzed in the whole aorta, and the degree of gastric inflammation was scored histologically in hematoxylin-eosin-stained stomach sections. The autoantibody titers to epitopes of oxidized LDL were also measured. Mice fed high-fat, high-cholesterol diets had a significantly higher incidence of gastritis than mice fed normal chow, 62% versus 5%, respectively (P<0.0001). This effect was specific for LDLR(-/-) mice, because no difference in gastritis was found in wild-type mice fed either diet. Animals with gastritis showed slightly more atherosclerosis than animals without gastritis: 16.3+/-6.4% versus 12.8+/-3.4% in males and 9.4+/-3.5% versus 6.5+/-3.3% in females. Cholesterol-fed mice also had significantly higher IgG autoantibody titers against modified LDL than normal chow-fed animals, but no difference was seen between the gastritis and nongastritis groups. We conclude that the standard high-fat, high-cholesterol diet commonly used in many murine models to induce atherosclerosis increased the incidence of gastritis significantly in LDLR(-/-) mice.
Laurila
A
A
Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0682, USA.
Cole
S P
SP
Merat
S
S
Obonyo
M
M
Palinski
W
W
Fierer
J
J
Witztum
J L
JL
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology; D002784:Cholesterol / Q000008:administration & dosage* / Q000097:blood; D004032:Diet / Q000009:adverse effects*; D005223:Fats / Q000008:administration & dosage*; D005260:Female; D005756:Gastritis / Q000209:etiology* / Q000473:pathology; D015994:Incidence; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics*; D013270:Stomach / Q000473:pathology; D015430:Weight Gain
D001323:Autoantibodies; D005223:Fats; D008055:Lipids; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein; D002784:Cholesterol