DIET-INDUCED TYPE-IV-LIKE HYPERLIPIDEMIA AND INCREASED BODY-WEIGHT ARE ASSOCIATED WITH CHOLESTEROL GALLSTONES IN HAMSTERS

Male Syrian hamsters (60-70 g) were fed purified diets containing 5% fat (American Fat Blend) and 15% fiber with or without 0.3% cholesterol (0.86 mg/kcal), for 12 weeks. Hamsters fed the cholesterol-supplemented challenge diet revealed a major increase in plasma triglyceride between 9 and 12 weeks, whereas plasma cholesterol (which reflected body weight dynamics) increased three-fold up to nine weeks and plateaued (342 +/- 22 vs. 122 +/- 5 mg/dL). The greatest increases in cholesterol occurred in the very low density lipoprotein (VLDL) and high density lipoprotein (HDL2) fractions. Gallstone incidence was similar (69% vs. 78%) for cholesterol-supplemented vs. control hamsters, but the type of stones differed. Of the cholesterol-supplemented hamsters with gallstones, 45% had cholesterol stones and 55% had pigment stones. Only pigment stones were seen in control hamsters. Hamsters with cholesterol stones were 25% heavier and transported most cholesterol in VLDL (33 +/- 5%), approximately double that in VLDL of cholesterol-supplemented hamsters with no stones (19 +/- 3%) or cholesterol-supplemented hamsters with pigment stones (21 +/- 3%). Hamsters with pigment stones or no stones (regardless of diet fed) transported the majority of their cholesterol in HDL2 (44%), whereas this figure was only 27% in hamsters that developed cholesterol stones. Thus pigment stones develop routinely in hamsters fed casein-based purified diets. Adding dietary cholesterol resulted in cholesterol gallstones only in those hamsters that gained the most weight and whose terminal VLDL/HDL cholesterol ratio exceeded 1.0, not unlike the lipoprotein profile of obese humans who develop cholesterol gallstones.