Several investigators have reported that feeding a semi-synthetic diet of
casein and
dextrose to New Zealand White (NZW) rabbits will increase total serum
cholesterol concentration, principally through an increase in the
beta-lipoprotein fractions, thereby creating a useful model for
atherosclerosis research. Although there is evidence to suggest that the
dextrose/
casein diet alters
low-density lipoprotein receptor and
bile acid clearance of
cholesterol, the underlying mechanism is not completely understood. The effects of the diet on the overall physiology of the rabbit have received little attention. In this study feeding a diet of
casein and
dextrose of male NZW rabbits for 4 weeks resulted in changes in the serum
lipid concentrations. During that time the rabbits fed the
dextrose/
casein diet gained less weight than did control rabbits. In the test diet rabbits, liver
aspartate and
alanine transaminase activities were increased from baseline values of 27 +/- 2 U/L and 89 +/- 9 U/L respectively to 112 +/- 21 U/L and 281 +/- 34 U/L respectively, then returned to the high end of the reference range. Necropsy findings included
hepatomegaly caused by vacuolar hepatopathy in 19 or 20 experimental rabbits; rabbits fed the control diet had no hepatic lesions. Ultrastructural analysis revealed that enlargement of the liver cells was due to
glycogen deposition. Adrenal glands from animals fed the experimental diet had a minimal change in the size of the adrenocortical cells consisting of slight ballooning and rarefaction of the cytoplasm. In a second study the level of
dietary fiber was doubled. This resulted in a three-fold increase in
lipid concentrations, compared with the fivefold increase in the first study. The liver
enzyme activities were increased to the same extent as in the first study. Histologic changes were comparable to those in the first study. The activity of hepatic
cholesterol 7alpha-hydroxylase was 3.7 +/- 0.4 pmol/min/mg of
protein, compared with the control value of 7.7 +/- 1.1 pmol/min/mg of
protein (P < 0.05) in the second study. The improved rate of
weight gain and the lesser increase in total serum
cholesterol concentration in the second study with increased
dietary fiber suggest that two separate activities may be involved. Although the level of
dietary fiber may be related to
weight gain and total serum
cholesterol values, the relation to the decrease in liver
transaminase activities in study 1 was probably coincidental. It appears that the
dextrose/
casein diet causes decreased activity of hepatic
cholesterol 7alpha-hydroxylase, which could cause a decrease in the biliary excretion of
cholesterol.