Mechanism of Triglyceridemia in Hypercholesterolemic Rabbits

Abstract

To elucidate mechanisms responsible for the increased plasma triglyceride (TG) which occurs in diet-induced hypercholesterolemia in rabbits, albino rabbits were fed a 3% cholesterol diet for various durations, and the following determinations were carried out: plasma lipid levels; turnover rate of plasma TG (labeled very low density lipoprotein, or glycerol-2-3 H method); lipoprotein lipase activity of the heart and plasma; fatty acid and acetate incorporation into TG in the liver (homogenates and slices). Plasma levels of both free and esterified cholesterol and phospholipid increased rapidly, while TG increased relatively slowly during cholesterol feeding without change in hepatic TG synthesis. The fractional turnover was, on the other hand, depressed within a week. The decrease in plasma TG in response to a heparin injection was less in hypercholesterolemic rabbits than in normal animals. However, the measured activity of heart lipoprotein lipase of cholesterol-fed rabbits was higher than that of the control group. When the effects of two substrates (very low density lipoprotein from normo-and from hypercholesterolemic plasma) were compared, the apparent activity was lower with the latter. The degree of this inhibition was proportional to the amount of cholesterol in the lipoproteins. The inhibition of lipoprotein lipase activity was also observed with the addition of cholesterol to activated Ediol, but not with addition of esterified cholesterol. Lineweaver-Burk plots were constructed using partially purified plasma lipoprotein lipase, and Km values for Ediol, Ediol plus protamine sulphate, and Ediol plus cholesterol were calculated. The presence of cholesterol in the substrate of lipoprotein lipase competitively inhibits the enzyme activity, and this is the mechanism of hyperglyceridemia observed in diet-induced hypercholesterolemic rabbits. ADDITIONAL KEY WORDS plasma lipoprotein lipase very low density lipoprotein plasma triglyceride turnover heart lipoprotein lipase cholesterol inhibition of lipoprotein lipase hepatic triglyceride synthesis • There are a number of clinical entities which accompany hypercholesterolemia, hyperglyceridemia, and defective postheparin lipolytic activity (1-4). Experimentally, when rabbits are fed a diet containing a high cholesterol content, not only does the plasma concentration of cholesterol increase, but an From the

Characteristics of mitochondrial and microsomal monoacyl- and diacyl-glycerol 3-phosphate biosynthesis in rabbit heart

“…Chloroform-methanol extraction procedures (Folch et al, 1957;Bligh & Dyer, 1959;Hajra et al, 1968;Eibl et al, 1969;Huang & Kako, 1970) constantly produced a high control value in the presence of subcellular fractions before incubation. Radioactivity was high and variable, even when the tissue fraction was omitted from the incubation mixture, which was probably due to non-specific binding of albumin (Barden & Cleland, 1969).…”

“…30-60°C)-diethyl ether-acetic acid (40:10:1, by vol.) (Possmayer & Mudd, 1971;Huang & Kako, 1970). The phospholipid and the neutral lipid fractions were eluted with chloroformmethanol (1: 1, v/v); the eluates were evaporated to a small volume under N2, and re-chromatographed in another system for further identification (see below).…”

Clearing-factor lipase in obese–hyperglycaemic mice (ob/ob)

“…In the present study the clearing-factor lipase activity in heart and adipose tissue from obese mice has been measured by a new assay procedure. In addition the plasma concentration of cholesterol and triglycerides, both of which may induce changes in the activity of clearing-factor lipase (Fielding, 1970;Huang & Kako, 1970;Shafrir & Biale, 1970), have been measured in an attempt to determine what modifiers of clearing-factor lipase are responsible for the changes in activity observed under different physiological conditions.…”

Effects of e99 yolk and moctamide on serum lipids in man

“…A pure type of hypercholesterolemia with normal tri glyceride level is known. However, it has been demonstrated that prolonged feeding of high cholesterol diet induces the elevation of serum triglyceride in rabbits 14 and that high concentration of serum cholesterol inhibits lipoprotein li- Daily oral administration of 300 mg of moctamide completely inhibited the elevation of serum cholesterol due to the egg yolk feeding. In the case of two subjects, serum cholesterol was lower than initial levels after the drug, though the same amount of egg yolk was ingested in this period (Table III).…”