title: Plasma clearance and net uptake of alpha-tocopherol and low-density lipoprotein by tissues in WHHL and control rabbits.
abstract: The mechanism(s) of uptake of vitamin E (alpha-tocopherol) by tissues is poorly understood. It has, however, been suggested from studies in vitro that the apolipoprotein B/E (apo B/E) receptor pathway for low-density lipoprotein (LDL) may be involved. To investigate the role of the apo B/E receptor pathway in vivo, we have studied the transport and uptake of alpha-tocopherol by tissues in Watanabe Heritable Hyperlipidaemic (WHHL) rabbits, which lack functional LDL (apo B/E) receptors, and controls. [3H]alpha-Tocopherol incorporated within LDL labelled with [14C]sucrose was used in these studies, as this enabled the uptake of both alpha-tocopherol and LDL to be studied independently. The principal findings were as follows. (1) Concentrations of the circulating lipids (including alpha-tocopherol) and LDL were increased and the plasma fractional disappearance rates of alpha-tocopherol and LDL decreased in the WHHL rabbits. (2) The WHHL rabbits clear more LDL and alpha-tocopherol from the circulation than controls do, because of their increased pool sizes of alpha-tocopherol and LDL. (3) The lipoprotein composition of the WHHL rabbits differed from that of the controls, and there was exchange of alpha-tocopherol between the lipoprotein fractions in vivo and in vitro. (4) High-affinity apo B/E receptors were not essential for the uptake of alpha-tocopherol by tissues. (5) Evidence from the plasma-clearance and tissue data suggest that alpha-tocopherol can be taken up by tissues in association with, and also independent of, LDL. We conclude that there are several different mechanisms for the uptake of alpha-tocopherol by tissues, which include receptor-dependent and receptor-independent pathways, independent transport and co-transport of alpha-tocopherol and LDL, and uptake from a number of different lipoproteins.
authors.affiliation: Department of Vitamin Research, F. Hoffmann-La Roche Ltd., Basle, Switzerland.
authors.forename: W
authors.initials: W
authors.lastname: Cohn
authors.forename: M A
authors.initials: MA
authors.lastname: Goss-Sampson
authors.forename: H
authors.initials: H
authors.lastname: Grun
authors.forename: D P
authors.initials: DP
authors.lastname: Muller
mesh_terms: D000818:Animals; D001692:Biological Transport; D006949:Hyperlipidemias / Q000378:metabolism / Q000662:veterinary; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism; D018110:Receptors, Lipoprotein; D013395:Sucrose / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism*
chemical_list: D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; C032531:apolipoprotein B,E receptor; D014810:Vitamin E; D013395:Sucrose