Impaired very low-density lipoprotein-triglyceride catabolism in acute and chronic fructose-fed rats.

Very low-density lipoprotein (VLDL)-triglyceride (TG) catabolism was compared in rats given chow and either a 10% fructose (F) or 10% glucose (G) drinking solution for both acute (A) (16 h) and chronic (C) (14 days) periods. VLDL-TG were labeled in F and G donor rats using different isotopic forms of glycerol. A mixture of the VLDLs was injected into F and G recipients and the decline in plasma TG radioactivities used as a measure of clearance. VLDL-TG from F donors was cleared more slowly than VLDL-TG from G donors. In F recipients, the half-life of VLDL-TG from either F or G donors was longer than that in G fed recipients. VLDL from the AF group, had a lower apoprotein E-to-C apoprotein ratio (E/C) than VLDL from the AG group. VLDL from both F groups had a lower E/C than did that from control rats. The E/C negatively correlated with plasma VLDL-TG. CF and CG VLDL had elevated CIII0 and lower CIII3 levels compared with their respective A groups and controls. The ratio of VLDL apoprotein B100, B95, and B48 did not differ between treatments. AF and AG VLDL were larger and enriched in TG compared with control or the CF and CG groups. The saturated fatty acid-to-unsaturated fatty acid ratio in VLDL-TG was higher in the G groups and AF group compared with controls. The present study suggests that the E/C may be lowered as a result of F consumption, thereby contributing to the impairment in VLDL-TG removal.

Metabolism of the apolipoprotein B-containing lipoproteins.

This chapter was designed to describe the approaches one can take to study the metabolism of the apoB-containing particles in vivo. The focus has been to blend (1) what is the current tracer kinetics analysis methodology and (2) what are the current experimental protocols being used into a total picture so that the experimentalist wishing to perform such studies may have a better perspective of the strong points and pitfalls of this important experimental tool. Hence, these points have been summarized from the point of view of what caveats are associated with each methodology. Recognition of these is essential to avoid reaching potentially erroneous conclusions. More important, attention has been focused on the realization that certain methodologies can be chosen depending upon what questions are being asked. Finally, areas where future development is needed in order to proceed to the next level of understanding are pointed out in the context of using tracer kinetic analysis as an integral part of a total experimental design.

The independent synthesis of intermediate density lipoproteins in type III hyperlipoproteinemia.

The kinetics of VLDL (Sf 60-400) and IDL (Sf 12-60) B apoprotein were examined in five type III hyperlipoproteinemic subjects. The production rates for B apoprotein were significantly greater in the IDL fraction than in VLDL. Precursor-product relationships between VLDL and IDL B apoprotein illustrated that a significant proportion of IDL B apoprotein was derived from some source other than VLDL catabolism. These observations indicated that, in the five individuals studied, an 'unusual' B apoprotein synthetic pathway operated whereby B apoprotein was directly entering the IDL fraction. Furthermore, this second pathway resulted in an overproduction of IDL B apoprotein and possibly was the major defect leading to the development of the type III hyperlipoproteinemia lipid profile. In two subjects who were restudied following hormonal treatment (estrogen or thyroxine replacement) and in whom the type III hyperlipoproteinemia lipid profile no longer existed, it was found that the pathway for direct synthesis of IDL B apoprotein had been abolished. From these studies we have concluded that a pathway for the direct synthesis of IDL B apoprotein operates in type III hyperlipoproteinemics and it is a major causative factor in the development of the IDL accumulation characteristic of this metabolic disorder.

Improved method for quantitation of B apoprotein in plasma lipoproteins by electroimmunoassay.

The B apoprotein occurs in a wide range of plasma lipoproteins, which are heterogenous both with respect to size and to composition. Immunochemical recognition of the apoprotein is influenced by the nature of the particle in which the apoprotein is found, presumably due to the masking of the antigenic sites by lipoprotein lipid. Consequently, it is difficult to provide suitable standards for use in routine electroimmunoassay procedures of the B apoprotein, particularly for triacylglycerol-rich lipoproteins. We have devised a procedure whereby lipoprotein samples, independent of their initial size and composition, are reduced, by use of a bacterial lipase, to a common size and composition, which is almost identical to that of the standard. This permits an assay that may be easily used routinely. It provides a far more reliable estimate of the absolute B apoprotein mass in plasma lipoproteins of the very-low- and low-density lipoprotein spectrum than has been previously available.