Kw. Huggins et al., Determination of the tissue sites responsible for the catabolism of large high density lipoprotein in the African green monkey, J LIPID RES, 41(3), 2000, pp. 384-394
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 h
ypothesized that these terminal particles were the end product of HDL metab
olism and, as such, would be cleared preferentially br 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 wer
e isolated, without ultracentrifugation, by size exclusion and immunoaffini
ty chromatography and radiolabeled crith either the residualizing compound,
I-125-labeled tyramine cellobiose (TC), or with I-131, After injection int
o recipient animals, the plasma die-away of the radiolabels tvas followed f
or 12 or 24 h, after which the animals were killed and tissues cr ere colle
cted for determining radiolabel sites of catabolism. The plasma die-away of
the I-125-labeled TC-LpA-I and I-131-labeled LpA-I doses was similar sugge
sting that the TC radiolabeling did not modify the metabolism of the large
LpA-I: dose. The liver, adrenal, kidney and spleen had the greatest accumul
ation 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 le
ss 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 f
at type on the tissue accumulation of large LpA-I. We conclude that the liv
er is the primary site of catabolism of large LpA-I in the African green mo
nkey.