Abstract
A major proportion of triglycerides in plasma triglyceride-rich lipoproteins (TRL) are removed in peripheral tissues by lipoprotein lipase, and hypothetically a minor proportion can also be removed by whole-lipoprotein particle uptake. This second removal pathway has not previously been directly demonstrated in humans. Simultaneous blood samples were drawn from arterialized blood, a vein draining the subcutaneous abdominal adipose tissue, and a deep antecubital vein of the forearm to provide arterio-venous gradients from blood-draining adipose tissue and muscle in seven male subjects. The men were given a fat-rich mixed meal containing vitamin A and the triglyceride and retinyl palmitate (RP) concentrations were quantified in the plasma. Density gradient ultracentrifugation was used to isolate TRL fractions, in which triglycerides, RP, apoB-48, and apoB-100 were quantified. There was clearance of triglycerides in muscle and adipose tissue and, in addition, removal of RP. By analysis of the TRL subfractions, the RP removal was likely to be confined to the largest chylomicron remnant particles. For the Sf > 400 fraction, the area under curve (AUC) relative to arterial for triglycerides were 79% (66-91%) and 81% (72-89%) in adipose tissue and muscle venous outflow, respectively (each P < 0.02 versus arterial). The corresponding values for RP were 87% (73-101%) and 85% (69-100%), respectively, (each P < 0.05 versus arterial). In the Sf 60-400 fraction there was further uptake of triglycerides, but not of RP. We hypothesize that the periphery could be of importance for removal of the largest chylomicron remnants, as their size might partially exclude them penetrating the fenestrated hepatic sinusoidal endothelium to reach the hepatic chylomicron remnant receptors.
Highlights
A major proportion of triglycerides in plasma triglyceride-rich lipoproteins (TRL) are removed in peripheral tissues by lipoprotein lipase, and hypothetically a minor proportion can be removed by whole-lipoprotein particle uptake
Based on calculations of triglyceride areas under curve (AUC), on average 7-9% of the plasma triglycerides were extracted during passage through the tissues (Table l ), the relative extraction was lower in the fasting state and the beginning of the postprandial state, compared to the late postprandial phase, which exhibited an extraction greater than 10% (Fig. 1)
The present work shows the expected clearance of triglycerides in muscle and adipose tissue and, in addition, tissue removal of several markers for triglyceriderich lipoproteins (TRL) particles, i.e., retinyl palmitate (RP),apoB-100,and apoB-48.In posprandial samples the lipoprotein particle removal was confined to the largest chylomicron remnant particles
Summary
A major proportion of triglycerides in plasma triglyceride-rich lipoproteins (TRL) are removed in peripheral tissues by lipoprotein lipase, and hypothetically a minor proportion can be removed by whole-lipoprotein particle uptake. This second removal pathway has not previously been directly demonstrated in humans. By analysis of the TRL subfractions, the RP removal was likely to be confined to the largest chylomicron remnant particles. For the Sf > 400 fraction, the area under curve (AUC) relative to arterial for triglycerides were 79% (66-91%) and 81% (7249%) in adipose tissue and muscle venous outflow, respectively The VLDL receptor, which is a nonhepatic receptor recognizing apoE as a ligand, has been shown to be expressed on endothelial cells (9,lO).Mice with a targeted disruption of the gene coding for the VLDL receptor do not develop hypertriglyceridemia, even after provocation with a carbohydrate-rich diet, but their total body weight and adipose tissue mass are slightly decreased compared to normal mice [11]
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