Yoshimi Kishimoto

Tocotrienol Suppresses Adipocyte Differentiation and Akt Phosphorylation in 3T3-L1 Preadipocytes

In vivo studies show that alpha-tocotrienol and gamma-tocotrienol accumulate in adipose tissue. Furthermore, a recent study reports that the oral administration of gamma-tocotrienol from a tocotrienol-rich fraction from palm oil (TRF) decreases body fat levels in rats. The objective of this study was to evaluate the effect of TRF and its components on adipocyte differentiation in 3T3-L1 preadipocytes, which differentiated into adipocytes in the presence of 1.8 micromol/L insulin. TRF suppressed the insulin-induced mRNA expression of adipocyte-specific genes such as PPARgamma, adipocyte fatty acid-binding protein (aP2), and CCAAT/enhancer-binding protein-alpha (C/EBPalpha) compared with the differentiation of 3T3-L1 preadipocytes into adipocytes only in the presence of insulin. To confirm the suppressive effect of TRF, the major components of TRF, such as alpha-tocotrienol, gamma-tocotrienol, and alpha-tocopherol, were investigated. Alpha-tocotrienol and gamma-tocotrienol decreased the insulin-induced PPARgamma mRNA expression by 55 and 90%, respectively, compared with insulin, whereas alpha-tocopherol increased the mRNA expression. In addition, gamma-tocotrienol suppressed the insulin-induced aP2 and C/EBPalpha mRNA expression, triglyceride accumulation, and PPARgamma protein levels compared with insulin. The current results also revealed that gamma-tocotrienol inhibited the insulin-stimulated phosphorylation of Akt but not extracellular signal-regulated kinase (ERK)1/2 in the insulin signaling pathway of 3T3-L1 preadipocytes. Thus, the antiadipogenic effect of TRF depends on alpha-tocotrienol and gamma-tocotrienol, and gamma-tocotrienol may be a more potent inhibitor of adipogenesis than alpha-tocotrienol. Therefore, the results of this study suggest that tocotrienol suppresses insulin-induced differentiation and Akt phosphorylation in 3T3-L1 preadipocytes. Furthermore, tocotrienol could act as an antiadipogenic vitamin in the nutrient-mediated regulation of body fat through its effects on differentiation.

Pleiotropic preventive effects of dietary polyphenols in cardiovascular diseases.

Polyphenols are common constituents of the diet, and research on their health benefits has developed quickly over the past few years. Our purpose is to review recent findings highlighting daily dietary polyphenol intake and the diverse function of polyphenols and their possible relationships to cardiovascular disease (CVD). Several cohort studies have reported an inverse relationship between the daily consumption of polyphenols and CVD risk. Many studies showed that beverages could be a large source of polyphenols. Our previous findings provide that Japanese people intake polyphenols mainly from beverages, especially coffee and green tea (in descending order of polyphenol content). Many kinds of polyphenols act as an antioxidant against low-density lipoprotein oxidation, which is known to promote atherosclerosis. Recent accumulating evidence suggests that dietary polyphenols could exert their cardioprotective actions through their potential to improve metabolic disorder and vascular inflammation. These findings raise the possibility that polyphenols have a wide variety of roles in the intestine, liver and vascular tissue. In addition to identifying mechanisms of polyphenol bioactivity by basic research, much more epidemiological and clinical evidence linking reduced cardiovascular risk with dietary polyphenols intake are needed.

Sweet potato (Ipomoea batatas L.) leaves suppressed oxidation of low density lipoprotein (LDL) in vitro and in human subjects

Sweet potato (Ipomoea batatas L.) leaves are consumed as vegetables around the world, especially in Southeast Asia. The aim of this study was to investigate the inhibitory effect of sweet potato leaves on low-density lipoprotein oxidation in vitro and in human subjects. We compared the antioxidant activity of 8 kinds of sweet potato leaves. Every sweet potato leaf had high radical scavenging activity and prolonged a lag time for starting low-density lipoprotein oxidation in vitro. We found that sweet potato leaves contained abundant polyphenol compounds and the radical scavenging activity and prolongation rate of lag time were highly correlated with total polyphenol content. We also confirmed that thiobarbituric acid reactive substances production was increased in endothelial cell-mediated low-density lipoprotein oxidation, which was decreased by treatment with sweet potato leaves. We further measured the low-density lipoprotein oxidizability in 13 healthy volunteers after their intake of 18 g of “Suioh”, raw sweet potato leaves. “Suioh” prolonged a lag time for starting low-density lipoprotein oxidation and decreased low-density lipoprotein mobility. These results suggest that sweet potato leaves have antioxidant activity leading to the suppression of low-density lipoprotein oxidation.

Effects of magnesium on postprandial serum lipid responses in healthy human subjects

Postprandial hyperlipidaemia has been recognised to be a risk factor for atherosclerosis development. Epidemiological and animal studies have shown that Mg intake is inversely associated with some risk factors of atherosclerosis, including lipid metabolism. The present study was performed to determine the effects of Mg supplementation on postprandial responses in serum lipid levels. We used bittern (Nigari, in Japanese), a natural MgCl(2) solution from sea or salt lake water, for Mg supplementation. In a two-way, randomised, crossover study, sixteen healthy male volunteers consumed 30 g butter with or without 5 ml bittern containing 500 mg of Mg. Fasting and postprandial blood samples were taken 2, 3, 4 and 6 h after ingestion. Postprandial lipid responses were evaluated by serum TAG, chylomicron TAG, apo-B48, remnant-like particle cholesterol (RLP-C) and NEFA concentrations. We found that the serum and the chylomicron TAG responses after the fat load were reduced and delayed by Mg supplementation. The concentrations of apo-B48 (P < 0.05), RLP-C (P < 0.05) and NEFA (P < 0.05) were significantly lower at 2 h after the fat-with-Mg meal compared with the fat-only meal. The present study indicated that Mg supplementation could inhibit fat absorption and improve postprandial hyperlipidaemia in healthy subjects.

Potential Anti-Atherosclerotic Properties of Astaxanthin

Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed.

Estimated Dietary Polyphenol Intake and Major Food and Beverage Sources among Elderly Japanese

Estimating polyphenol intake contributes to the understanding of polyphenols’ health benefits. However, information about human polyphenol intake is scarce, especially in the elderly. This study aimed to estimate the dietary intake and major sources of polyphenols and to determine whether there is any relationship between polyphenol intake and micronutrient intake in healthy elderly Japanese. First, 610 subjects (569 men, 41 women; aged 67.3 ± 6.1 years) completed food frequency questionnaires. We then calculated their total polyphenol intake using our polyphenol content database. Their average total polyphenol intake was 1492 ± 665 mg/day, the greatest part of which was provided by beverages (79.1%). The daily polyphenol intake differed largely among individuals (183–4854 mg/day), also attributable mostly to beverage consumption. Coffee (43.2%) and green tea (26.6%) were the major sources of total polyphenol; the top 20 food items accounted for >90%. The polyphenol intake did not strongly correlate with the intake of any micronutrient, suggesting that polyphenols may exert health benefits independently of nutritional intake. The polyphenol intake in this elderly population was slightly higher than previous data in Japanese adults, and beverages such as coffee and green tea contributed highly to the intake.

Green tea catechins prevent low-density lipoprotein oxidation via their accumulation in low-density lipoprotein particles in humans

Green tea is rich in polyphenols, including catechins which have antioxidant activities and are considered to have beneficial effects on cardiovascular health. In the present study, we investigated the effects of green tea catechins on low-density lipoprotein (LDL) oxidation in vitro and in human studies to test the hypothesis that catechins are incorporated into LDL particles and exert antioxidant properties. In a randomized, placebo-controlled, double-blind, crossover trial, 19 healthy men ingested green tea extract (GTE) in the form of capsules at a dose of 1 g total catechin, of which most (>99%) was the gallated type. At 1 hour after ingestion, marked increases of the plasma concentrations of (-)-epigallocatechin gallate and (-)-epicatechin gallate were observed. Accordingly, the plasma total antioxidant capacity was increased, and the LDL oxidizability was significantly reduced by the ingestion of GTE. We found that gallated catechins were incorporated into LDL particles in nonconjugated forms after the incubation of GTE with plasma in vitro. Moreover, the catechin-incorporated LDL was highly resistant to radical-induced oxidation in vitro. An additional human study with 5 healthy women confirmed that GTE intake sufficiently increased the concentration of gallated catechins, mainly in nonconjugated forms in LDL particles, and reduced the oxidizability of LDL. In conclusion, green tea catechins are rapidly incorporated into LDL particles and play a role in reducing LDL oxidation in humans, which suggests that taking green tea catechins is effective in reducing atherosclerosis risk associated with oxidative stress.

Milk-derived peptide Val-Pro-Pro (VPP) inhibits obesity-induced adipose inflammation via an angiotensin-converting enzyme (ACE) dependent cascade.

SCOPE This study aimed to examine the effects of Val-Pro-Pro (VPP), a food-derived peptide with an angiotensin-converting enzyme (ACE) inhibitory property, on obesity-linked insulin resistance, and adipose inflammation in vivo and in vitro. METHODS AND RESULTS C57BL/6J mice were fed high-fat high-sucrose diet and VPP (0.1% in water) for 4 months. For in vitro analysis, coculture of 3T3-L1 adipocytes overexpressing either ACE (3T3-ACE) or green fluorescent protein (3T3-GFP) and RAW264 macrophages was conducted with VPP. In diet-induced obese mice, VPP improved insulin sensitivity, concomitant with a significant decrease in tumor necrosis factor α (TNF-α) and IL-1β expression in adipose tissue, with a tendency (p = 0.06) toward decreased CC chemokine ligand 5 expression. Additionally, VPP administration inhibited macrophage accumulation and activation in fat tissues. In vitro, VPP attenuated TNF-α mRNA induced by ACE overexpression in 3T3-L1 adipocytes. TNF-α and IL-1β expression decreased following VPP treatment of RAW264 macrophage and 3T3-ACE adipocyte cocultures, but not in RAW264-3T3-GFP adipocyte cocultures. CONCLUSION Our data suggest that VPP inhibits adipose inflammation in the interaction between adipocytes and macrophages, acting as an ACE inhibitor, thereby improving obesity-related insulin resistance. Thus, ingestion of VPP may be a viable protective and therapeutic strategy for insulin resistance and obesity-associated adipose inflammation.

Coffee and beverages are the major contributors to polyphenol consumption from food and beverages in Japanese middle-aged women.

Food and beverages rich in polyphenols have been shown to reduce the risk of non-communicable diseases. The present study estimated polyphenol levels and consumption from food and beverages in Japanese women. Randomly recruited housewives living in the area around Tokyo (n 109; aged 21–56 years; Group 1) recorded all beverages and foods they ingested for 7 d, and the total polyphenol (TP) consumption was estimated based on the TP content of each item measured with a modified Folin–Ciocalteu method. For Group 1, TP was consumed at 841 (sd 403) mg/d (range 113–1759 mg/d), and beverages were a larger source of TP (79 %) than food (21 %). The largest single source of TP was coffee at 47 %, followed by green tea, black tea, chocolate, beer and soya sauce, at 16, 5·7, 3·3, 3·2 and 3·1 %, respectively. In terms of food groups, cereals/noodles, vegetables, fruits, beans and seeds, and seasonings (except for soya sauce) contributed 5·0, 4·0, 1·4, 1·8 and 2·4 %, respectively. Another group of housewives who consumed at least one cup of coffee per d were separately recruited (n 100; Group 2) in the same area. Their consumption of TP was higher at 1187 (sd 371) mg/d (range 440–2435 mg/d) than Group 1 (P < 0·001), and the difference mostly came from the coffee consumption. We conclude that not food but beverages, especially coffee, may be the major contributor to TP consumption in Japanese women.

Consumption of polyphenol-rich juar tea increases endothelium-bound extracellular superoxide dismutase levels in men with metabolic syndrome: link with LDL oxidizability

Endothelium-bound extracellular superoxide dismutase (eEC-SOD), a major antioxidative enzyme in the vasculature, is involved in anti-atherogenesis by inhibiting low-density lipoprotein (LDL) oxidation. The objective was to investigate whether the polyphenol-rich juar tea had beneficial effects on LDL oxidation and eEC-SOD levels in patients with metabolic syndrome (MetS). A total of 20 men with MetS participated in a randomized cross-over trial, comparing consumption of five cups/day of juar tea with that of a polyphenol-poor tea, barley tea, for 4 weeks. Although there was no change in LDL oxidizability after consumption of either tea, juar tea significantly increased eEC-SOD levels by 16% (p < 0.05), whereas barley tea significantly decreased levels by 15% (p < 0.05). It is noteworthy that the changes in eEC-SOD were positively associated with those in LDL oxidizability after tea consumption (r 2 = 0.11, p < 0.05). Tea polyphenols may provide anti-atherosclerotic effects by inhibiting LDL oxidation through EC-SOD bound to the endothelium.