Loci of catabolism of β-very low density lipoprotein in vivo delineated with a residualizing label, ¹²⁵I-dilactitol tyramine

β-Very low density lipoprotein (β-VLDL) may be a major atherogenic lipoprotein, and knowledge of the sites of its catabolism should facilitate elucidation of mechanisms important in the regulation of its plasma concentrations. In this study, catabolic sites of β-VLDL have been delineated in normolipidemic rabbits with a novel, radioiodinated, residualizing label, ¹²⁵I-dilactitol tyramine (¹²⁵I-DLT). Comparative studies of β-VLDL and low density lipoprotein catabolism were performed with ¹²⁵I-DLT conjugated to each lipoprotein and with lipoproteins iodine-labeled conventionally. Conjugation did not alter size distributions or charge characteristics of lipoprotein particles. The overall processing (binding and degradation) of lipoproteins by cultured rabbit skin fibroblasts was not influenced by ¹²⁵I-DLT derivatization, suggesting that attachment of the label did not influence cell receptor-lipoprotein interactions. Furthermore, although degradation products of ¹²⁵I-lipoproteins leaked out of the cells and into the medium, the degradation products of ¹²⁵I-DLT lipoproteins were retained by the cells. The principal catabolic site of β-VLDL in normolipidemic rabbits was found to be the liver with 54 ± 4% of injected ¹²⁵I retained in this organ 24 h after injection of ¹²⁵I-DLT-β-VLDL. When catabolism was normalized to tissue weight, the liver and adrenals were found to be approximately equally active in the metabolism of β-VLDL. In agreement with results of other studies with residualizing labels, the principal organ of catabolism of ¹²⁵I-DLT-LDL in vivo was the liver. The adrenals were the most highly catabolizing organ when results were normalized for tissue weight. The quantitative differences observed in the tissue distributions of injected ¹²⁵I-DLT-β-VLDL and ¹²⁵I-DLT-low density lipoprotein suggested that a significant proportion of β-VLDL is removed by tissues before conversion to low density lipoprotein.