Regulatory mechanisms to control tissue α-tocopherol

Abstract

To test the hypothesis that hepatic regulation of α-tocopherol metabolism would be sufficient to prevent over-accumulation of α-tocopherol in extrahepatic tissues and that administration of high doses of α-tocopherol would up-regulate extrahepatic xenobiotic pathways, rats received daily subcutaneous injections of either vehicle or 0.5, 1, 2, or 10 mg α-tocopherol/100 g body wt for 9 days. Liver α-tocopherol increased 15-fold in rats given 10 mg α-tocopherol/100 g body weight (mg/ 100 g) compared with controls. Hepatic α-tocopherol metabolites increased with increasing α-tocopherol doses, reaching 40-fold in rats given the highest dose. In rats injected with 10 mg/100 g, lung and duodenum α-tocopherol concentrations increased 3-fold, while α-tocopherol concentrations of other extrahepatic tissues increased 2-fold or less. With the exception of muscle, daily administration of less than 2 mg/100 g) failed to increase α-tocopherol concentrations in extrahepatic tissues. Lung cytochrome P450 3A and 1A levels were unchanged by administration of α-tocopherol at any dose. In contrast, lung P-glycoprotein (MDR-1) levels increased dose dependently and expression of this xenobiotic transport protein was correlated with lung α-tocopherol concentrations (R 2 = 0.88, P < 0.05). Increased lung MDR1 may provide protection from exposure to environmental toxins by increasing alveolar space α-tocopherol.

Scientific Opinion on Dietary Reference Values for vitamin E as α‐tocopherol

“…By the action of lipoprotein lipase (LPL), extra-hepatic tissues may take up part of the α-tocopherol transported in chylomicrons, while the remnant chylomicrons transport α-tocopherol to the liver. (Traber, 2007;Wu and Croft, 2007;Gee, 2011).…”

“…Once secreted into the circulation, VLDL are converted into intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL) by the action of LPL, and the excess of VLDL surface components, including α-tocopherol, is transferred to high-density lipoproteins (HDL) (Traber, 2007;Wu and Croft, 2007;Gee, 2011).…”

Mechanisms for the prevention of vitamin E excess

“…It should be noted that the vitamin E-related substrates for the sulfotransferase and the transporters are unknown; the transporters are not involved in lipoprotein uptake. The net effect of these processes is, in the face of a high infl ux of ␣ -tocopherol into the liver, to limit circulating ␣ -tocopherol to a 2-to 4-fold increase ( 174 ), to increase ␣ -CEHC excretion in urine ( 109,176 ), and potentially to increase both ␣ -tocopherol and ␣ -CEHC excretion in bile and thereby limit the delivery of ␣ -tocopherol to extrahepatic tissues ( 177 ).…”

Present trends in vitamin E research

“…Genetic factors are now identified to play a role in the physiological control of the intestinal absorption and transfer of vitamin E to chylomicrons and intestinal HDL [47,48], and thus in the liver uptake and incorporation of vitamin E into nascent VLDL for peripheral tissues distribution [49]. Genetic factors are also at the basis of vitamin E catabolism and biliary elimination by the ABC transporters [50].…”