The New Zealand white (NZW) rabbit fed a 0.1%
cholesterol-enriched diet (CD) typically responds (normoresponsive, NR) by quickly developing
hypercholesterolemia. To study the underlying mechanisms responsible for the widespread phenomenon of inter-individual variability of response to
dietary cholesterol, a unique
hypercholesterolemia-resistant (RT) rabbit model was developed. These animals were utilized to investigate selected potential mechanisms that might enable the RT animal to compensate for
dietary cholesterol overload. When rabbits were fed the low-
cholesterol stock diet, there was no significant difference in the plasma
cholesterol concentrations of the NR and the RT animals. However, a significant rise was observed in the NR rabbits within 1 month of their being placed on the
cholesterol-enriched diet; the plasma
cholesterol concentration of the RT animals was not affected. During consumption of the
cholesterol diet the
cholesterol absorption rate was somewhat greater in the NR rabbits (P less than 0.05), whereas intestinal transit times and the fecal excretion of neutral
steroids were substantially the same in both groups. In contrast, the fecal
bile acid excretion of the RT animals was more than twice as great (P less than 0.0001) as that of the NR animals. We conclude that the response to
dietary cholesterol is a heritable trait in these rabbits and that, although less
dietary cholesterol was absorbed by the RT animals, it appears that a major mechanism controlling plasma
cholesterol levels involves the rate of conversion of
cholesterol to
bile acids and their subsequent excretion.