Clearance from plasma of triacylglycerol and cholesteryl ester after intravenous injection of chylomicron-like lipid emulsions in rats and man

Abstract

Chylomicrons transport fat and cholesterol via lymphatic vessels from the intestine into the bloodstream. The understanding of the metabolism of chylomicrons in man has been slowed by the difficulty of obtaining lymph chylomicrons for experimental studies. Acceptable methods for the study of chylomicron clearance in man are required, because the metabolism of chylomicrons may be abnormal in diseases such as diabetes mellitus. Metabolism of chylomicrons may also play a role in the development of atherosclerosis. In the present work, lipid emulsions were used as a physical model of chylomicrons. Triacylglycerol-rich lipid emulsions labelled with tracer amounts of radioactive triolein and cholesteryl oleate were prepared by sonication and purified by density gradient ultracentrifugation, then injected into unanaesthetized rats and normal human subjects. Plasma radioactivities were measured for 30 min in rats and 90 min in human subjects. Rat lymph chylomicrons were also injected into rats for comparison with the clearance of the lipid emulsions. The plasma clearance data for triacylglycerols and cholesteryl esters were fitted with a kinetic model using the SAAM/CONSAM programs. Multiple studies analysis of the individual studies in each group was used to obtain estimates of the parameter average values and variabilities. The plasma residence times of the lipid labels were obtained from the fitted clearance data. Our results suggest that information about chylomicron metabolism in man can be obtained by analysis of the plasma clearance data following the injection of suitably labelled chylomicron-like lipid emulsions. Our data provide a baseline for comparisons with individuals having abnormalities of lipid metabolism or risk factors for arteriosclerosis.

Relationships in women between body mass index and the intravascular metabolism of chylomicron-like emulsions

“…The emulsion shows plasma halflives of cholesteryl esters and triglycerides that are equivalent to those of lymph chylomicrons in rats and subjects. 17,25 Since only minimal amounts of cholesteryl esters shift from the emulsion particles, this moiety is indeed a marker of the removal of the remnant particles. 17,25 Since the emulsions are injected intravenously, the gastrointestinal component is bypassed allowing straightforward calculation of the plasma kinetic data.…”

“…17,25 Since only minimal amounts of cholesteryl esters shift from the emulsion particles, this moiety is indeed a marker of the removal of the remnant particles. 17,25 Since the emulsions are injected intravenously, the gastrointestinal component is bypassed allowing straightforward calculation of the plasma kinetic data. Injected in minimal lipid amounts after a 12 h fasting, the emulsion does not disturb the VLDL metabolism.…”

“…The safety of the radioactive dose injected into the subjects was warranted according to radioprotection regulations 24 as described elsewhere. 17 Compartmental analysis Emulsion removal from the plasma was evaluated by compartmental analysis according to a modification of the model proposed by Redgrave et al 25 Briefly, four compartments were employed to estimate the kinetic parameters for both 14 C-Cholesteryl-oleate (CO) and 3 H-Triolein (TO) tracers. Plasma hydrolysis and removal of native chylomicrons, as well as chylomicron-like emulsions, displayed a rapid initial decay followed by a slow removal phase.…”

Evaluation of the “Olson Equation”, an Isotope Dilution Method for Estimating Vitamin A Stores

“…Absorption efficiency could be assessed using a dual isotope method, modeled on a test developed to determine cholesterol absorption in rats [27]. In the dual label method, subjects would be given an oral dose containing one stable isotope of vitamin A and an intravenous dose of artificial chylomicrons [28,29] containing a different stable isotope. Once the labels have equilibrated, the ratio of the fraction of dose of the two isotopes in plasma would refl ect absorption of the oral dose, under the assumption that the intravenous dose represents 100 % "absorption."…”

Lipid and apolipoprotein B48 transport in mesenteric lymph and the effect of hyperphagia on the clearance of chylomicron-like emulsions in insulin-deficient rats

“…To control for the first possibility, chylomicron-like emulsions free of exogenous apolipoproteins were used to assess chylomicron clearance. The plasma clearance of the chylomicron-like emulsions is comparable to lymph chylomicrons [32]. A group of diabetic rats fed ad libitum was compared with a group pair-fed with matched non-diabetic control rats.…”