Abstract
Cholesterol-fat feeding is associated with unusual alterations in the composition of plasma lipoproteins in alloxan-diabetic rabbits. In the present study plasma lipoprotein lipid and apoprotein composition was studied before and after 48 hr of fasting in cholesterol-fed diabetic and control rabbits in order to further characterize these alterations. Compared with control rabbits, the diabetic rabbits had similar plasma cholesterol levels, but 100-fold higher triglyceride levels prior to fasting. These plasma lipids were distributed mainly to large, Sf greater than 400 plasma lipoproteins in the diabetic rabbits, and to beta-VLDL in control rabbits. Sf greater than 400 lipoproteins, VLDL, IDL, LDL, and HDL from diabetic rabbits had triglyceride as the predominant lipoprotein core lipid. Sf greater than 400 lipoproteins and VLDL from diabetic rabbits had lesser amount of apoprotein E, and greater amounts of apoproteins A-I, A-IV, and B-48 as percent of total apoprotein mass in comparison with control rabbits. Fasting reduced plasma triglyceride levels by 55% in diabetic rabbits. Sf greater than 400 lipoprotein and VLDL triglyceride content decreased but remained a major core lipid. Fasting eliminated apoproteins A-I and A-IV from Sf greater than 400 lipoproteins and VLDL, but had no significant effect on apoB-48 content. Insulin treatment of the diabetic rabbits reduced plasma triglyceride by approximately 90% resulting in cholesteryl ester-rich particles reassembling beta-VLDL both in the Sf greater than 400 lipoprotein and VLDL fractions. These results indicate that the alterations in plasma lipoproteins in cholesterol-fed diabetic rabbits result from the presence in the d less than 1.006 g/ml plasma lipoprotein class of partially metabolized, intestinally derived particles.
Highlights
These plasma lipids were distributed mainly to large, Sf > 400 plasma lipoproteins in the diabetic rabbits, and to P-very low density lipoproteins (VLDL) in control rabbits
In a recent study we re-examined this animal model, and confirmed the results of the earlier studies showing protection towards cholesterol-induced atherosclerosis, hypertriglyceridemia, and a n accumulation of d < 1.019 g/ml plasma lipoproteins [4].We examined the chemical and physical properties of the d < 1.019 g/ml plasma lipoprotein fraction and found that most of the plasma triglyceride and cholesteryl esters coexisted in the core of a relatively homogenous population of large particIes
Plasma cholesterol levels in the diabetic rabbits were comparable to those of the non-diabetic animals despite the fact that they consumeda diet with onlyone-third the cholesterol content
Summary
New Zealand white rabbits, weighing between 2.4 and 3.1 kg, were purchased from Pine Acres Farm, Brattleboro, VT. A separate group of cholesterol-fed diabetic rabbits was treated with protamine-zinc insulin (1.0 U/kg per day, subcutaneously as a single dose) These animals were fed the same diet as the other diabetic rabbits for 7 days prior to, and for 10 days following, the initiation of insulin treatment. They were fasted overnight prior to collecting blood for plasma lipid and lipoprotein analysis before and after the interval of insulin treatment. Quantitative estimates of differences in aproprotein content of Sf > 400 and VLDL lipoproteins between diabetic and non-diabetic rabbits were obtained by scanning 10% polyacrylamide gels with a densitometer at 560 nm Test was used to test for differences between diabetic and control groups, and paired t-tests were used to test for significant effects of fasting
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