Saiko Ikeda

Comparative effects of flaxseed and sesame seed on vitamin E and cholesterol levels in rats

Flaxseed and sesame seed both contain more than 40% fat, about 20% protein, and vitamin E, mostly γ-tocopherol. Furthermore, both contain considerable amounts of plant lignans. However, flaxseed contains 54% α-linolenic acid, but sesame seed only 0.6%, and the chemical structures of flaxseed and sesame lignans are different. In this study, we investigated the differential effects of flaxseed and sesame seed on plasma and tissue γ-tocopherol, TBARS, and cholesterol concentrations. Rats were fed experimental diets for 4 wk: vitamin E-free, (-VE), γ-tocopherol, flaxseed (FS), sesame seed (SS), flaxseed oil (FO), FO with sesamin (FOS), and defatted flaxseed (DFF). SS and FOS diets induced significantly higher γ-tocopherol concentrations in plasma and liver compared with FS, FO, and DFF diets. Groups fed FS, FO, and FOS showed lower plasma total cholesterol compared with the SS and DFF groups. Higher TBARS concentrations in plasma and liver were observed in the FS and FO groups but not in the FOS groups. These results suggest that sesame seed and its lignans induced higher γ-tocopherol and lower TBARS concentrations, whereas flaxseed lignans had no such effects. Further, α-linolenic acid produced strong plasma cholesterol-lowering effects and higher TBARS concentrations.

Effects of various tocopherol-containing diets on tocopherol secretion into bile.

Abstractγ-Tocopherol is abundant in common vegetable oil, but its concentration in plasma and liver is much lower than that of α-tocopherol. Discrimination between different forms of tocopherol is thought to take placevia the hepatic α-tocopherol transfer protein (α-TTP). γ-Tocopherol, with a low binding capacity to α-TTP, is thought to be excretedvia the bile. Our previous studies showed that γ-tocopherol administered with sesame seed exhibits significantly higher concentrations in the plasma and liver of rats than γ-tocopherol alone. Thus, we attempted to confirm whether a much higher amount of γ-tocopherol rather than γ-tocopherol would be secreted in the bile, and whether sesame seed would suppress the secretion of γ-tocopherol. In one experiment, we examined the concentrations of α-or γ-tocopherol in the plasma, liver, and bile of rats fed diets containing 300 mg/kg of α-tocopherol, 300 mg/kg of γ-tocopherol, or 300 mg/kg each of α-tocopherol+γ-tocopherol, and in the other experiment, we compared the γ-tocopherol concentrations of rats fed a diet of γ-tocopherol alone to those of rats fed a γ-tocopherol+sesame seed diet (each diet contained 300 mg/kg γ-tocopherol). The bile collection was done over 6 h. The γ-tocopherol concentration in the bile was markedly lower than that of α-tocopherol, paralleling the concentrations in the plasma and liver. Intake of α-tocopherol and γ-tocopherol together further lowered the concentration of γ-tocopherol in the bile as well as in the plasma and liver, compared to the intake of γ-tocopherol alone. The γ-tocopherol concentration in the bile, as well as in the plasma and liver, was markedly higher in the sesame seed-fed group than in the γ-tocopherol alone group. We found that the concentrations of α- or γ-tocopherol in the bile showed a good correlation with the concentrations of α- or γ-tocopherol in the liver, though the concentrations in the bile were substantially lower than those in the liver. These findings suggest that secretion into the bile is not a major metabolic route of α- or γ-tocopherol.

Effect of sesaminol on plasma and tissue α-tocopherol and α-tocotrienol concentrations in rats fed a vitamin E concentrate rich in tocotrienols

We have shown that sesame lignans added to rat diet resulted in significantly greater plasma and tissue concentrations of α- and γ-tocopherol concentrations in supplemented rats than in rats without supplementation. In the present studies we examined whether sesaminol, a sesame lignan, enhances tocotrienol concentrations in plasma and tissues of rats fed diets containing a tocotrienol-rich fraction of palm oil (T-mix). In Ex-periment 1, effects of sesaminol on tocotrienol concentrations in plasma, liver, and kidney were evaluated in rats fed diets containing 20 mg/kg of T-mix (20T) and 50 mg/kg of T-mix (50T) with or without 0.1% sesaminol. Although the T-mix contained 23% α-tocopherol, 22% α-tocotrienol, and 34% γ-tocotrienol, α-tocopherol constituted most or all of the vitamin E in plasma and tissue (from 97% in kidney to 100% in plasma), with no or very little α-tocotrienol and no γ-tocotrienol at all. Addition of sesaminol to the T-mix resulted in significantly higher plasma, liver, and kidney α-tocopherol concentrations compared to values for T-mix alone. Further, T-mix with sesaminol resulted in significantly higher α-tocotrienol concentrations in kidney, although the concentration was very low. In Experiment 2, we examined whether sesaminol caused enhanced absorption of α-tocopherol and α-tocotrienol in a dosage regimen supplying T-mix and sesaminol on alternating days and observed significantly higher levels of α-tocopherol and α-tocotrienol in rats fed sesaminol, even without simultaneous intake, compared to those in rats without sesaminol. In Experiment 3, α-tocopherol was supplied to the stomach with and without sesaminol, and α-tocopherol concentrations in the lymph fluid were measured, α-Tocopherol concentrations were not different between groups. These results indicated that sesaminol produced markedly higher α-tocopherol concentrations in plasma and tissue and significantly greater α-tocotrienol concentrations in kidney and various other tissues, but the concentrations of α-tocotrienol were extremely low compared to those of α-tocopherol (Exps. 1 and 2). However, the sesaminol-induced increases of α-tocopherol and α-tocotrienol concentrations in plasma and tissue were not caused by their enhanced absorption since sesaminol did not enhance their absorption.

Complexation of Tocotrienol with γ-Cyclodextrin Enhances Intestinal Absorption of Tocotrienol in Rats

To determine the bioavailability of tocotrienol complex with γ-cyclodextrin, the effects of tocotrienol/γ-cyclodextrin complex on tocotrienol concentration in rat plasma and tissues were studied. Rats were administered by oral gavage an emulsion containing tocotrienol, tocotrienol with γ-cyclodextrin, or tocotrienol/γ-cyclodextrin complex. At 3 h after administration, the plasma γ-tocotrienol concentration of the rats administered tocotrienol/γ-cyclodextrin complex was higher than that of the rats administered tocotrienol and γ-cyclodextrin. In order to determine the effect of complexation on tocotrienol absorption, rats were injected with Triton WR1339, which prevents the catabolism of triacylglycerol-rich lipoprotein by lipoprotein lipase, and then administered by oral gavage an emulsion containing tocotrienol, tocotrienol with γ-cyclodextrin, or tocotrienol/γ-cyclodextrin complex. The plasma γ-tocotrienol concentration of the Triton-treated rats administered tocotrienol/γ-cyclodextrin complex was higher than that of the other Triton-treated rats. These results suggest that complexation of tocotrienol with γ-cyclodextrin elevates plasma and tissue tocotrienol concentrations by enhancing intestinal absorption.

Dietary Sesame Seed and Its Lignan, Sesamin, Increase Tocopherol and Phylloquinone Concentrations in Male Rats

We have shown that intake of sesame seed and its lignan increases vitamin E concentrations and decreases urinary excretion levels of vitamin E metabolites in male Wistar rats, suggesting inhibition of vitamin E catabolism by sesame lignan. The aim of this study was to examine whether dietary sesame seed also increased vitamin K concentrations, because its metabolic pathway is similar to that of vitamin E. To test the effect of sesame lignan on vitamin K concentrations, male Wistar rats were fed a control diet or a diet with 0.2% sesamin (a sesame lignan) for 7 d in experiment 1. Liver phylloquinone (PK), menaquinone-4 (MK-4), and γ-tocopherol were greater in rats fed sesamin than in control rats. To test the effect of sesame seed on vitamin K concentrations, male Wistar rats were fed a control diet or a diet with 1, 5, or 10% sesame seed for 3 d in experiment 2. Liver and kidney PK and γ-tocopherol but not MK-4 were greater in rats fed sesame seed than in control rats, although differences in dietary amounts of sesame seed did not affect the PK concentrations. For further confirmation of the effect of sesame seed, male Wistar rats were fed a control diet or a diet with 20% sesame seed for 40 d in experiment 3. Kidney, heart, lung, testis, and brain PK and brain MK-4 were greater in rats fed sesame seed than in control rats. The present study revealed for the first time, to our knowledge, that dietary sesame seed and sesame lignan increase not only vitamin E but also vitamin K concentrations in rat tissues.

Excess α-tocopherol decreases extrahepatic phylloquinone in phylloquinone-fed rats but not menaquinone-4 in menaquinone-4-fed rats

SCOPE The effects of vitamin E on vitamin K metabolism were elucidated by comparing the effect of tocopherol intake on vitamin K concentrations in rats fed phylloquinone (PK) or menaquinone (MK)-4. METHODS AND RESULTS Initially, the dietary effect of RRR-α-tocopherol, but not RRR-γ-tocopherol, in decreasing extrahepatic PK concentrations was confirmed. Subsequently, rats were fed a PK or MK-4-containing diet (0.75 mg/kg) with RRR-α-tocopherol (0, 10, 50, or 500 mg/kg) for 6 weeks. In rats fed PK, α-tocopherol consumption decreased PK in kidney, lung, heart, muscle, testis, and brain but not in serum and liver. However, in rats fed MK-4, α-tocopherol consumption did not decrease MK-4 in serum and tissues. Finally, vitamin K- and E-depleted rats were administered PK or MK-4 (0.2 mg) with RRR-α-tocopherol (0, 1, or 10 mg) by gavage. After PK administration, α-tocopherol was observed to decrease PK in kidney, adrenal gland, lung, testis, and brain but not in serum and liver, whereas, after MK-4 administration, α-tocopherol did not affect MK-4 in serum and tissues. CONCLUSION Excess α-tocopherol decreased extrahepatic PK in rats fed PK but not MK-4 in rats fed MK-4.

Time-restricted feeding suppresses excess sucrose-induced plasma and liver lipid accumulation in rats

The etiology of metabolic syndrome involves several complicated factors. One of the main factors contributing to metabolic syndrome has been proposed to be excessive intake of sucrose, which disturbs hepatic lipid metabolism, resulting in fatty liver. However, the mechanism by which sucrose induces fatty liver remains to be elucidated. Considering feeding behavior important for metabolism, we investigated whether time-restricted feeding of high sucrose diet (HSD), only in the active phase (the dark phase of the daily light/dark cycle), would ameliorate adverse effects of sucrose on lipid homeostasis in rats. Male Wistar rats, fed either an ad libitum (ad lib.) or time-restricted control starch diet (CD) or HSD were investigated. Rats fed ad lib. (CD and HSD) completed approximately 20% of food intake in the daytime. Time-restricted feeding did not significantly suppress total food intake of rats. However, time-restricted feeding of HSD significantly suppressed the increased plasma triglyceride levels. Moreover, time-restricted feeding also ameliorated HSD-induced liver lipid accumulation, whereas circadian oscillations of liver clock gene or transcriptional factor gene expression for lipid metabolism were not altered significantly. These results demonstrated that restricting sucrose intake only during the active phase in rats ameliorates the abnormal lipid metabolism caused by excess sucrose intake.

α-Tocopherol Intake Decreases Phylloquinone Concentration in Bone but Does Not Affect Bone Metabolism in Rats

Previous studies have shown that α-tocopherol intake lowers phylloquinone (PK) concentration in some extrahepatic tissues in rats. The studys aim was to clarify the effect of α-tocopherol intake on vitamin K concentration in bone, as well as the physiological action of vitamin K. Male Wistar rats were divided into 4 groups. Over a 3-mo period, the K-free group was fed a vitamin K-free diet with 50 mg RRR-α-tocopherol/kg, the E-free group was fed a diet containing 0.75 mg PK/kg without vitamin E, the control group was fed a diet containing 0.75 mg PK/kg with 50 mg RRR-α-tocopherol/kg, and the E-excess group was fed a diet containing 0.75 mg PK/kg with 500 mg RRR-α-tocopherol/kg. PK concentration in the liver was higher in E-excess rats than in E-free rats, was lower in the tibias of control rats than in those of E-free rats, and was lower in E-excess rats than in control rats. Menaquinone-4 (MK-4) concentration in the liver was higher in E-excess rats than in E-free and control rats. However, MK-4 concentrations in the tibias of E-free, control, and E-excess rats were almost the same. Blood coagulation activity was lower in K-free rats than in the other rats but was not affected by the level of α-tocopherol intake. Additionally, dietary intake of PK and α-tocopherol did not affect uncarboxylated-osteocalcin concentration in the serum, femur density, or expression of the genes related to bone resorption and formation in the femur. These results suggest that α-tocopherol intake decreases PK concentration in bone but does not affect bone metabolism in rats.