α‐Tocopherol does not Accelerate Depletion of γ‐Tocopherol and Tocotrienol or Excretion of their Metabolites in Rats

Abstract

From an enzyme kinetic study using rat liver microsomes, α-tocopherol has been suggested to accelerate the other vitamin E catabolism by stimulating vitamin E ω-hydroxylation, the late limiting reaction of the vitamin E catabolic pathway. To test the effect of α-tocopherol on catabolism of the other vitamin E isoforms in vivo, we determined whether α-tocopherol accelerates depletion of γ-tocopherol and tocotrienol and excretion of their metabolites in rats. Male Wistar rats were fed a γ-tocopherol-rich diet for 6 weeks followed by a γ-tocopherol-free diet with or without α-tocopherol for 7 days. Intake of γ-tocopherol-free diets lowered γ-tocopherol concentrations in serum, liver, adrenal gland, small intestine, and heart, but there was no effect of dietary α-tocopherol on γ-tocopherol concentrations. The level of urinary excretion of γ-tocopherol metabolite was not affected by dietary α-tocopherol. Next, the effect of α-tocopherol on tocotrienol depletion was examined using rats fed a tocotrienol-rich diet for 6 weeks. Subsequent intake of a tocotrienol-free diet with or without α-tocopherol for 7 days depleted concentrations of α- and γ-tocotrienol in serum and tissues, which was accompanied by a decrease in the excretion of γ-tocotrienol metabolite. However, neither the tocotrienol concentration nor γ-tocotrienol metabolite excretion was affected by dietary α-tocopherol. These data showed that dietary α-tocopherol did not accelerate the depletion of γ-tocopherol and tocotrienol and their metabolite excretions, suggesting that the positive effect of α-tocopherol on vitamin E ω-hydroxylase is not sufficient to affect the other isoform concentrations in tissues.

α-Tocomonoenol Is Bioavailable in Mice and May Partly Be Regulated by the Function of the Hepatic α-Tocopherol Transfer Protein

“…Overall, αT concentrations in tissues were about 10-fold lower than the values reported in tissues of mice and rats fed diets containing 30–100 mg αT per kg diet [ 7 , 13 , 16 , 18 , 25 ]. These low αT concentrations in tissues are more similar to values reported in mice and rats after feeding of αT-deficient or αT-free diets [ 16 , 25 , 28 ]. The unexpected depletion of αT and αT 1 from the livers of our mice was confirmed by GC/MS analyses (see Figure S1 , data interpretation based on a previous publication [ 29 ]).…”

“…αT concentrations in αT-fed TTP +/+ mice were in the order of adipose tissue > brain > heart > spleen > lungs > kidneys > small intestine > liver and reached 0.560 ± 0.065 μmol/L in blood ( Figure 4 ). Relatively high αT concentrations in adipose tissue were reported before [ 13 , 16 , 25 ] and explained by the comparably low turnover of adipocytes, which slowly accumulated and released αT [ 16 , 26 ]. Adipose tissue was also reported as the main storage for α- and γ-tocotrienols and marine-derived tocopherol [ 14 , 16 , 18 , 25 , 27 ].…”

“…It was previously reported that αT is secreted from the liver at a higher rate, thus possibly depleting the liver of αT when the intake of the vitamin is inadequate [ 26 , 30 ]. A complete reduction of αT in the liver was reported for TTP −/− mice fed a vitamin E-depleted diet from the age of 3 to 18 months [ 31 ], for male Wistar rats fed a diet containing < 0.4 μg/g αT for 6 weeks followed by an αT-free diet for 7 days [ 25 ], and an almost complete depletion of αT from the liver was observed in male Fisher 344 rats after 6 months feeding with an αT-deficient diet [ 32 ], as well as in male Wistar rats fed a vitamin E-free diet from 6 until 10 weeks old [ 16 ], but not in animals fed the recommended dietary dose of 30 mg/kg feed. The overall low αT and αT 1 values in the tissues and their complete depletion from the liver led us to question the stability of the congeners in the experimental diets and the resulting amounts fed to our mice (see Section 2.3 ).…”

Regulation of Obesity and Metabolic Complications by Gamma and Delta Tocotrienols

“…When rats were fed with an AIN93G (a purified rodent diet) diet mixed with 0.2% T3s (2.5% αT3, 92% γT3 and 4.2% δT3) for 13 weeks, the level of γT3 ranged between 164 and 597 nmol/g in different types of fat pads [55]. Uchida et al found that rats fed with a T3 mixture (33.9% αT3, 47.1% γT3 and 11% δT3) for six weeks followed by a vitamin E-depleted diet for one month, the αT3 and γT3 concentrations remained high in adipose tissue, indicating that αT3 and γT3 have slow degradation rates and that adipose tissue is a unique site to store T3s [56]. Dietary αTP is likely to counteract T3 accumulation in tissues, and it has been shown that 50 mg/kg αTP in the diet decreases αT3, but not γT3 accumulation in the adipose tissue of rats fed with a diet supplemented with 50 mg/kg αT3 or γT3 for eight weeks [56].…”

“…Uchida et al found that rats fed with a T3 mixture (33.9% αT3, 47.1% γT3 and 11% δT3) for six weeks followed by a vitamin E-depleted diet for one month, the αT3 and γT3 concentrations remained high in adipose tissue, indicating that αT3 and γT3 have slow degradation rates and that adipose tissue is a unique site to store T3s [56]. Dietary αTP is likely to counteract T3 accumulation in tissues, and it has been shown that 50 mg/kg αTP in the diet decreases αT3, but not γT3 accumulation in the adipose tissue of rats fed with a diet supplemented with 50 mg/kg αT3 or γT3 for eight weeks [56]. Accumulation of T3s in fat tissues indicates that the adipocytes may be the major site of action of T3s.…”