Diet‐induced type IV‐like hyperlipidemia and increased body weight are associated with cholesterol gallstones in hamsters

Abstract 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 (HDL 2 ) 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 HDL 2 (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.