HEPATIC AND ADRENAL CHANGES IN RABBITS ASSOCIATED WITH HYPERLIPIDEMIACAUSED BY A SEMISYNTHETIC DIET

Several investigators have reported that feeding a semi-synthetic diet of casein and dextrose to New Zealand White (NZW) rabbits will increa se total serum cholesterol concentration, principally through an incre ase in the beta-lipoprotein fractions, thereby creating a useful model for atherosclerosis research, Although there is evidence to suggest t hat the dextrose/casein diet alters low-density lipoprotein receptor a nd bile acid clearance of cholesterol, the underlying mechanism is not completely understood. The effects of the diet on the overall physiol ogy of the rabbit have received little attention, In this study feedin g a diet of casein and dextrose to male NZW rabbits for 4 weeks result ed in changes in the serum lipid concentrations. During that time the rabbits fed the dextrose/casein diet gained less weight than did contr ol rabbits. In the test diet rabbits, liver aspartate and alanine tran saminase activities were increased from baseline values of 27 +/- 2 Un and 89 +/- 9 U/L respectively to 112 +/- 21 U/L and 281 +/- 34 U/L re spectively, then returned to the high end of the reference range. Necr opsy findings included hepatomegaly caused by vacuolar hepatopathy in 19 of 20 experimental rabbits; rabbits fed the control diet had no hep atic lesions. Ultrastructural analysis revealed that enlargement of th e liver cells was due to glycogen deposition. Adrenal glands from anim als fed the experimental diet had a minimal change in the size of the adrenocortical cells consisting of slight ballooning and rarefaction o f the cytoplasm. In a second study the level of dietary fiber was doub led. This resulted in a threefold increase in lipid concentrations, co mpared with the fivefold increase in the first study. The liver enzyme activities were increased to the same extent as in the first study, H istologic changes were comparable to those in the first study. The act ivity of hepatic cholesterol 7 alpha-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 o f weight gain and the lesser increase in total serum cholesterol conce ntration in the second study with increased dietary fiber suggest that two separate activities may be involved. Although the level of dietar y fiber may be related to weight gain and total serum cholesterol valu es, the relation to the decrease in liver transaminase activities in s tudy 1 was probably coincidental. It appears that the dextrose/casein diet causes decreased activity of hepatic cholesterol 7 alpha-hydroxyl ase, which could cause a decrease in the biliary excretion of choleste rol.