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 st udies. While developing a Helicobacter infection model in LDL receptor-nega tive (LDLR-/-) mice, we noticed that mice fed a high-fat, high-cholesterol diet often contracted gastritis independent of infection. To further invest igate 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 atheros clerosis was morphometrically analyzed in the whole aorta, and the degree o f gastric inflammation was scored histologically in hematoxylin-eos in-stai ned stomach sections. The autoantibody titers to epitopes of oxidized LDL w ere also measured. Mice fed high-fat, high-cholesterol diets had a signific antly higher incidence of gastritis than mice fed normal chow, 62% versus 5 %, respectively (P <0.0001). This effect was specific for LDLR-/- mice, bec ause 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 9.1 +/-3.5 % versus 6.5 +/-3.3% in females. Cholesterol-fed mice also had significantl y 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 commo nly used in many murine models to induce atherosclerosis increased the inci dence of gastritis significantly in LDLR-/- mice.