Original Article

Determination of the tissue sites responsible for the catabolism of large high density lipoprotein in the African green monkey

Correspondence to: John S. Parks

In vivo multicompartmental modeling of the turnover of HDL subfractions has suggested that HDL containing four molecules of apoA-I per particle and no other apolipoproteins (large LpA-I) are terminal particles in plasma. We hypothesized that these terminal particles were the end product of HDL metabolism and, as such, would be cleared preferentially by the liver. Thus, the purpose of this study was to determine: 1) the tissue sites of catabolism of large LpA-I in African green monkeys, and 2) whether saturated versus n;–6 polyunsaturated dietary fat affected tissue accumulation. Large LpA-I were isolated, without ultracentrifugation, by size exclusion and immunoaffinity chromatography and radiolabeled with either the residualizing compound, ¹²⁵I-labeled tyramine cellobiose (TC), or with ¹³¹I. After injection into recipient animals, the plasma die-away of the radiolabels was followed for 12 or 24 h, after which the animals were killed and tissues were collected for determining radiolabel sites of catabolism. The plasma die-away of the ¹²⁵I-labeled TC-LpA-I and ¹³¹I-labeled LpA-I doses was similar suggesting that the TC radiolabeling did not modify the metabolism of the large LpA-I dose. The liver, adrenal, kidney, and spleen had the greatest accumulation of large LpA-I degradation products on a per gram tissue basis. On a whole organ basis, the liver was the major site of large LpA-I degradation in both the 12-h (15.4 ± 0.3% of injected dose) and 24-h (9.1 ± 0.6% of injected dose) catabolic studies. The kidney, compared to the liver, had less uptake of large LpA-I radioactivity in either study (1.3 ± 0.4% and 1.2 ± 0.3% of injected dose). There was no apparent influence of dietary fat type on the tissue accumulation of large LpA-I.

We conclude that the liver is the primary site of catabolism of large LpA-I in the African green monkey.—Huggins, K. W., E. R. Burleson, J. K. Sawyer, K. Kelly, L. L. Rudel, and J. S. Parks. Determination of the tissue sites responsible for the catabolism of large high density lipoprotein in the African green monkey. J. Lipid Res. 2000. 41: 384;–394.

Supplementary key words: apoA-I, tyramine cellobiose, catabolism, LpA-I, SR-BI, ultracentrifugation

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