The major compensatory responses to increased cholesterol consumption are decreased cholesterol synthesis and increased cholesterol excretion through the bile either as free cholesterol or bile acids. The objective of this study was to test the hypothesis that biliary cholesterol excretion is increased in hamsters fed low levels of cholesterol reflecting normal human intake. The hypothesis was based on observations that hamsters generally resist changes in bile acid synthesis when fed large amounts of cholesterol; therefore, increased biliary cholesterol excretion represents a potentially significant pathway for elimination of excess cholesterol in this species. Hamsters were fed modified NIH-07 cereal-based diets containing 0.02%, 0.03%, and 0.05% cholesterol (0.04, 0.06, and 0.10 mg cholesterol/kcal, respectively). The primary response to increasing amounts of dietary cholesterol was downregulation of whole-body cholesterol synthesis, reduced from 3.93 ± 0.14 μmol · d-1 · 100 g-1 body weight in hamsters fed 0.02% cholesterol to 0.52 ± 0.14 μmol · d-1 · 100 g-1 in the 0.05% cholesterol group. Biliary cholesterol excretion was also slightly reduced in hamsters fed 0.05% cholesterol, whereas bile acid excretion was not altered by dietary cholesterol. Despite a pronounced downregulation of whole-body cholesterol synthesis, liver and plasma cholesterol concentrations increased in hamsters fed 0.05% cholesterol. The data indicate that increased biliary cholesterol excretion is not a major compensatory route of cholesterol excretion in hamsters consuming cholesterol. Furthermore, cholesterol added to the diet at 0.05% appears to be the approximate threshold at which compensatory mechanisms can prevent increases in liver and plasma cholesterol in male Syrian hamsters. Consequently, this species may be an appropriate animal model for 'hyperresponding' individuals in the human population.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism