The role of the low density lipoprotein receptor for alpha-tocopherol delivery to tissues

To study the role of the LDL receptor pathway for the maintenance of alpha-tocopherol concentrations in tissues of intact animals, we have compared vitamin E levels in plasma and tissues of normal rabbits and WHHL rabbits. WHHL rabbits are deficient in LDL receptor activity. For WHHL rabbits, alpha-tocopherol plasma concentrations were elevated to 10 times normal levels. When plasma lipoprotein profiles were analyzed by density gradient centrifugation, concentrations of VLDL, IDL, and LDL were increased in WHHL rabbits, and plasma alpha-tocopherol was only recovered in these fractions. In normal rabbits, plasma alpha-tocopherol was confined mainly to the HDL fraction; levels associated with LDL were markedly lower. Despite LDL receptor deficiency, alpha-tocopherol concentrations in various tissues of WHHL rabbits were not found to be reduced, with the exception of the adrenal. Vitamin E levels in muscle and kidney of WHHL rabbits exceeded those of normal animals. Our results demonstrate the importance of the LDL receptor pathway for vitamin E clearance in the normal rabbit, although at high LDL concentrations, alternative mechanisms may become more efficient for the delivery of vitamin E to tissues.