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Journal of Lipid Research, Vol. 40, 2234-2243, December 1999
Copyright © 1999 by Lipid Research, Inc.

Original Article

Apolipoprotein B overproduction by the perfused liver of the St. Thomas' mixed hyperlipidemic (SMHL) rabbit

Correspondence to: Chris J. Packard

The St. Thomas' mixed hyperlipidemic (SMHL) rabbit (previously St. Thomas' Hospital rabbit) is a putative model of familial combined hyperlipidemia (FCH). When fed a low (0.08%) cholesterol diet, it exhibits elevations in both plasma cholesterol and triglyceride compared to New Zealand White (NZW) controls. To determine the mechanism for this hyperlipidemia we studied the secretion of apolipoprotein B (apoB)-containing lipoproteins from perfused livers of both young and mature rabbits. During a 3-h perfusion we measured the total cholesterol and triglyceride content of the medium and the cholesterol, triglyceride, and apoB content of very low density lipoprotein (VLDL)₁ (S_f 60;–400), VLDL₂ (S_f 20;–60), intermediate (S_f 12;–20), and low (S_f 0;–12) density lipoproteins (IDL, LDL). Lipoprotein concentrations increased linearly throughout the perfusion period. The rate of cholesterol output was 3-fold higher (459 vs. 137 ng/g liver/min, P = 0.003) in SMHL versus NZW rabbits whilst that of triglyceride was similar (841 vs. 662 ng/g liver/min, NS). VLDL₁ cholesterol output was elevated 2-fold (232 vs. 123 ng/g liver/min, P < 0.05) and VLDL₂ + IDL + LDL cholesterol output, 4.5-fold (106 vs. 23 ng/g liver/min, P < 0.005) in SMHL versus NZW rabbits. ApoB output in VLDL1 was 38 ng/g liver per min in SMHL and 14 ng/g liver per min in NZW (NS). In SMHL VLDL₂ + IDL + LDL apoB was increased 9-fold at 53 versus 6 ng/g liver per min in NZW (P < 0.001).

We conclude that the SMHL rabbit overproduces apoB-containing lipoproteins particularly in the VLDL₂ + IDL + LDL fraction, a characteristic consistent with its use as a model of FCH.—Ardern, H. A., G. M. Benson, K. E. Suckling, M. J. Caslake, J. Shepherd, and C. J. Packard. Apolipoprotein B overproduction by the perfused liver of the St. Thomas' mixed hyperlipidemic (SMHL) rabbit. J. Lipid Res. 1999. 40: 2234;–2243.

Supplementary key words: liver perfusion, lipoprotein production, VLDL, IDL, LDL, apoB production, Froxfield Mixed hyperlipidemic rabbit, St. Thomas Hospital rabbit

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