High-fat, high-cholesterol diet increases the incidence of gastritis in LDL receptor-negative mice

Arterioscler Thromb Vasc Biol. 2001 Jun;21(6):991-6. doi: 10.1161/01.atv.21.6.991.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arteriosclerosis / pathology
  • Autoantibodies / immunology
  • Cholesterol / administration & dosage*
  • Cholesterol / blood
  • Diet / adverse effects*
  • Fats / administration & dosage*
  • Female
  • Gastritis / etiology*
  • Gastritis / pathology
  • Incidence
  • Lipids / blood
  • Lipoproteins, LDL / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, LDL / genetics*
  • Stomach / pathology
  • Weight Gain


  • Autoantibodies
  • Fats
  • Lipids
  • Lipoproteins, LDL
  • Receptors, LDL
  • oxidized low density lipoprotein
  • Cholesterol