Biomedical subjects
Publications and source records attributed to Ichiro Tokimitsu.
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BACKGROUND: The incidence of hyperlipidemia in children is increasing in Japan, but drug therapy for such children is limited. The ingestion of 4% phytosterols-containing diacylglycerol (PS/DAG) decreases serum total cholesterol and low density lipoprotein cholesterol (LDL-C) concentrations in adults. In the present study, we examined the effect of PS/DAG as part of a diet therapy in pediatric patients with hyperlipidemia. METHODS: Pediatric patients with hyperlipidemia with > or =5.18mmol (200 mg/dL) serum total cholesterol and/or >or =1.70mmol (150 mg/dL) triglycerides (N=22) ingested bread containing PS/DAG (total daily intake, 10g) for 6 months. Blood chemistry was examined prior to and 2, 4, 6 months after the initiation of ingestion, and 4 months after the ingestion period. RESULTS: No significant differences in energy intake or cholesterol intake during the study period were found. After 4 months of ingestion of PS/DAG, LDL-C, lipoprotein(a) [ Lp(a)], free fatty acids and total ketone bodies decreased significantly. In seven patients with familial hypercholesterolemia, total cholesterol and remnant-like lipoprotein particles (RLP)-cholesterol also significantly decreased in addition to LDL-C and Lp(a). CONCLUSIONS: PS/DAG improves serum lipid metabolism in pediatric patients with hyperlipidemia for whom drug therapy is limited, suggesting that PS/DAG may reduce the risk of developing various diseases induced by hyperlipidemia.
The diacylglycerol (DAG), a commonly used as a cooking oil in Japan, results in a lower elevation of serum triglyceride (TG) after ingestion compared to triacylglycerol (TAG). Postprandial hyperlipidemia (PPHL) and an increase in remnant lipoproteins (RLP) levels are risk factors for CAD, and a close relationship between PPHL and type 2 diabetes and/or insulin resistance has been reported. To evaluate the effect of DAG on PPHL in insulin resistance and glucose intolerance, 11 subjects with a normal glucose tolerance (NGT) and 14 subjects with IGT received oral fat tolerance test (OFTT) twice. They ingested emulsified test oils prepared with either DAG or TAG. In the IGT subjects, after the DAG and TAG load, the serum concentrations of TG, RLP-TG, and RLP-cholesterol increased throughout the 4-h study. The responses of these variables above baseline after the DAG load were significantly smaller than those after the TAG load (p<0.05). In contrast, in the NGT subjects, changes in these parameters were much smaller than those observed for IGT subjects. The difference in the integrated responses for serum RLP-cholesterol concentration during OFTT between DAG and TAG in all subjects can be easily explained by the integrated response of insulin rather than glucose during oral glucose tolerance test (r=0.7, p<0.01). DAG was more effective in insulin resistant and hyperinsulinemic participants regardless of glucose intolerance, and may be beneficial in reducing the extent of CAD risk in such individuals.
The effects of high-fat (HF) feeding on gene expression in the small intestine were examined using obesity-resistant A/J mice and obesity-prone C57BL/6J (B6) mice. Both strains of mice were maintained on low-fat (LF; 5% fat) or HF (30% fat) diets for 2 wk. Quantitative reverse transcription-PCR analysis revealed that lipid metabolism-related genes, including carnitine palmitoyltransferase (CPT) I, liver fatty acid binding protein, pyruvate dehydrogenase kinase-4, and NADP(+)-dependent cytosolic malic enzyme, were upregulated by HF feeding in both strains of mice. The upregulated gene expression levels were higher in A/J mice than in B6 mice, suggesting more active lipid metabolism in the small intestine of A/J mice. The prominent upregulation of the lipid metabolism-related genes were specific to the small intestine; the expression levels were little or unchanged in the liver, muscle, and white adipose tissue. The increase by HF feeding and predominant expression of the intestinal lipid metabolism-related genes in A/J mice were reflected in the enzyme activities; malic enzyme, CPT, and beta-oxidation activities were increased by HF feeding, and the upregulated malic enzyme and CPT activities were significantly higher in obesity-resistant A/J mice compared with those in obesity-prone B6 mice. These findings suggest that intestinal lipid metabolism is associated with susceptibility to obesity.
BACKGROUND: Diacylglycerol (DAG) suppresses the postprandial increase in serum triglycerides, and has antiobesity effects. On the other hand, plant sterol esters (PSE) lower serum cholesterol levels in hypercholesterolemia. Thus, DAG-containing PSE (PSE/DAG) would be expected to maintain an appropriate serum cholesterol level and decrease the risk of arteriosclerotic disorders. Several recent studies, however, report negative effects of PSE on serum fat-soluble (pro)vitamin levels. The objective of this study was to investigate the effect of PSE/DAG on serum retinol, beta-carotene, and alpha-tocopherol levels using a threefold excess of the effective dose obtained in our previous study. METHODS: A randomized placebo-controlled double-blind parallel study was performed in healthy and mildly hypercholesterolemic subjects, in which the subjects ingested 1.2 g PSE/30 g DAG for 2 weeks in the form of mayonnaise-type products. Triacylglycerol (TAG) mayonnaise was used as a control. RESULT: There were no subjective adverse effects or changes in serum retinol, alpha-tocopherol, and beta-carotene levels, abdominal symptoms, hematologic values, or blood biochemical values. CONCLUSION: Ingestion of a threefold excess of PSE/DAG for 2 weeks had no adverse effects compared to ingestion of conventional TAG mayonnaise.
Chlorogenic acid, a polyphenol found in coffee, has antihypertensive actions, but epidemiologic data on the effects of coffee on blood pressure are controversial. Specific coffee components that inhibit the hypotensive effect of chlorogenic acid and the physiologic mechanisms underlying the effects of coffee without these components were investigated. One component, hydroxyhydroquinone (HHQ), inhibited the hypotensive effects of chlorogenic acid in spontaneously hypertensive rats (SHR). The attenuation of hypertension by HHQ-free coffee was associated with nitric oxide, the suppression of mRNA expression of NAD(P)H oxidase, and the improvement in endothelium-dependent vasodilation in the aorta. Thus, HHQ-free coffee might regulate vascular tone by improving the bioavailability of nitric oxide in SHR.
A series of polyphenols known as catechins are abundant in green tea, which is consumed mainly in Asian countries. The effects of catechin-rich green tea extract (GTE) on running endurance and energy metabolism during exercise in BALB/c mice were investigated. Mice were divided into four groups: nonexercise control, exercise control (Ex-cont), exercise+0.2% GTE, and exercise+0.5% GTE groups. Treadmill running time to exhaustion, plasma biochemical parameters, skeletal muscle glycogen content, beta-oxidation activity, and malonyl-CoA content immediately after exercise were measured at 8-10 wk after the initiation of the experiment. Oxygen consumption and respiratory exchange ratio were measured using indirect calorimetry. Running times to exhaustion in mice fed 0.5% GTE were 30% higher than in Ex-cont mice and were accompanied by a lower respiratory exchange ratio, higher muscle beta-oxidation activity, and lower malonyl-CoA content. In addition, muscle glycogen content was high in the GTE group compared with the Ex-cont group. Plasma lactate concentrations in mice fed GTE were significantly lower after exercise, concomitant with an increase in free fatty acid concentrations. Catechins, which are the main constituents of GTE, did not show significant effects on peroxisome proliferator-activated receptor-alpha or delta-dependent luciferase activities. These results suggest that the endurance-improving effects of GTE were mediated, at least partly, by increased metabolic capacity and utilization of fatty acid as a source of energy in skeletal muscle during exercise.
The effects of DAG oil and TAG oil on impaired glucose tolerance in rats that were fed a diet containing high levels of sucrose were compared. Male Wistar rats (8 wk old and 32 wk old) were fed either high-sucrose (57.5% sucrose w/w) or control diets containing either 10% (w/w) DAG or TAG oil with a similar FA composition for 48 wk in 8-wk-old rats and for 24 wk in 32-wk-old rats. Plasma lipids, the size of the islets of Langerhans, and insulin, glucose, and adipocytokine levels were measured. An oral glucose tolerance test (OGTT) was carried out during the study period. For rats in both age groups that were fed a high-sucrose diet, the DAG oil group had lower plasma glucose and insulin response in an OGTT, and lower homeostasis model assessment-R levels, than the TAG oil group. Furthermore, in 8-wk-old rats that were fed a high-sucrose diet, the DAG oil group accumulated less visceral fat and showed suppressed decreases [corrected] of plasma adiponectin and [corrected] increases of plasma insulin, leptin, and the size of islet of Langerhans compared with the TAG oil group. No difference in the OGTT was found between the DAG and TAG oil groups in either age group of rats fed a control diet. In conclusion, these results suggest that DAG oil ingestion prevents the high-sucrose-diet-induced development of impaired glucose tolerance compared with TAG oil ingestion.
OBJECTIVE: The objective of the present study was to verify the effect of a dietary oil, consisting mainly of diacylglycerol (DAG) oil, in a typical meal on postprandial changes in serum triacylglycerol (TAG) and remnant-like particle cholesterol (RLP-C) compared with dietary triacylglycerol (TAG) oil. METHODS: In a double-blind, randomized, crossover design, 43 healthy Japanese men and women ingested test meals (2093 kJ of energy, 30 g of protein, 19 g of lipids, and 51 g of carbohydrates) containing 10 g of DAG oil (DAG meal) or TAG oil (TAG meal). Blood samples were collected in a fasting state (0 h) and at 2, 3, 4, and 6 h after ingestion of the meal. RESULTS: Postprandial TAG, RLP-C, and chylomicron TAG concentrations were significantly lower after the DAG meal compared with the TAG meal. In 29 subjects with fasting serum TAG levels of at least 1.13 mmol/L (100 mg/dL), differences in postprandial serum changes between meal types were even more remarkable and the incremental areas under the response curve (0 to 6 h) for serum TAG and RLP-C concentrations after the DAG meal were significantly smaller than those after the TAG meal. CONCLUSIONS: These results suggest that DAG oil in the daily diet is useful for the prevention of postprandial hyperlipidemia and related disorders.
OBJECTIVE: The objective of this study was to investigate the effective dose of plant sterol ester (PSE)-enriched diacylglycerol (DAG) oil for healthy subjects with mild hypercholesterolemia. METHODS: A randomized, placebo-controlled, double-blind, parallel study was performed in patients with mild hypercholesterolemia; 0.0, 0.3, 0.4, and 0.5 g of PSE was dissolved in 15 g of a DAG-containing mayonnaise-type product; and 15 g/d of the product was administered 4 wk. RESULTS: Total serum cholesterol levels were significantly decreased as a result of the ingestion of at least 0.4 g/d of PSE, and serum low-density lipoprotein cholesterol levels were significantly decreased by the ingestion of at least 0.3 g/d of PSE. CONCLUSIONS: Daily ingestion of 15 g of DAG plus mayonnaise containing at least 0.4 g/d of PSE for 4 wk may significantly decrease cholesterol.
INTRODUCTION: Prevention of arterial thrombotic diseases has high priority in developed countries. An appropriate diet is thought to be the best way to prevent or reduce the risk of mortality from such diseases. The aim of the present study was to evaluate the effect of diacylglycerol (DAG)-rich diets on arterial thrombosis. MATERIAL AND METHODS: Diet-sensitive congenital apolipoprotein E (ApoE) and LDL receptor (LDLR) double deficient mice were used. Thrombosis was assessed by the rate and extent of thrombus formation in the carotid artery of mice after laser irradiation. Plasma total cholesterol and triglyceride levels were measured by enzymatic assays. Four kinds of diets were used: high fat (Western-style) diet contained 20% fat (w/w) and 0.05% cholesterol (w/w); the TAG-rich and the DAG-rich high fat diet contained 20% TAG or DAG oil (w/w) with very similar fatty acid composition and 0.05% cholesterol ; Low fat (Japanese-style) diet contained 7% fat, without cholesterol. These diets were on the basis of AIN93G and were given to mice for 8 weeks from 6 weeks of age. RESULTS: Western-style high fat and TAG-rich high fat diets significantly increased thrombogenicity compared with low fat diet. DAG-rich high fat diet showed the lowest value, and the extent of thrombogenicity was equivalent to the low fat diet group. Fasting plasma total cholesterol level of DAG-rich high fat and low fat diet groups were significantly lower than that of TAG-rich high fat and high fat diet groups. Fasting plasma triglyceride levels in DAG-rich high fat diet group were significantly lower than in the TAG-rich high fat diet group. CONCLUSIONS: Dietary DAG but not TAG oil extenuates arterial thrombus formation. The mechanism of this effect is unclear and further investigated.
In the present study, we characterized diacylglycerol (DAG) oil in terms of energy metabolism by comparing oxygen consumption and respiratory quotient (RQ), as well as blood parameters, in rats after administration of emulsions containing either DAG or triacylglycerol (TAG) with similar fatty acid composition. Twelve male Wistar rats (250-280 g) were acclimatized, and then catheterized into the stomach, and held individually in Bollman restraining cages. After 24 hours fasting, each emulsion containing either DAG or TAG (10 g/kg body weight) was infused. Oxygen consumption and fat oxidation in the DAG group gradually increased after administration of the DAG emulsion and became significantly higher than those of the TAG group. RQ in both groups dropped after administration of emulsion, but the values of the DAG group were significantly lower than that of the TAG group. The postprandial serum triglyceride level was significantly increased from 60 minutes after administration in the TAG group, and 240 minutes in the DAG group, compared to the preprandial level. The serum triglyceride level tended to be lower in the DAG group than in the TAG group at 60 minutes and thereafter, and the statistical difference between the TAG and DAG groups was significant at 300 minutes after administration. These results suggest that DAG oil infusion might lead to higher energy expenditure and lipids oxidation compared to TAG oil with a similar fatty acid composition.
BACKGROUND AND OBJECTIVES: Epidemiologic studies indicate that ingestion of vegetables and fruit inhibits the development of cardiovascular disease. Chlorogenic acids are abundant phenolic compounds contained in vegetables and fruits, but the impact of dietary chlorogenic acids on vascular function in hypertension is not known. We therefore examined the effects of 5-caffeoylquinic acid (CQA), a representative chlorogenic acid, on blood pressure and vascular function in age-matched normotensive Wistar-Kyoto rats and spontaneously hypertensive rats. METHODS AND RESULTS: A single ingestion of CQA (30-600 mg/kg) reduced blood pressure in spontaneously hypertensive rats, an effect that was blocked by administration of a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester. When spontaneously hypertensive rats were fed diets containing 0.5% CQA for 8 weeks (approximately 300 mg/kg per day), the development of hypertension was inhibited compared with the control diet group. CQA ingestion increased urinary excretion of nitric oxide metabolites and decreased urinary excretion of hydrogen peroxide; decreased NADPH-dependent superoxide anion production in the aorta, suggesting that dietary CQA inhibited vascular NADPH oxidase activity; significantly improved acetylcholine-induced endothelium-dependent vasodilation in the aorta; and markedly reduced the degree of immunohistochemical staining for nitrotyrosine and media hypertrophy in aorta sections. In contrast, CQA had no effects in Wistar-Kyoto rats. CONCLUSIONS: Dietary CQA reduces oxidative stress and improves nitric oxide bioavailability by inhibiting excessive production of reactive oxygen species in the vasculature, and leads to the attenuation of endothelial dysfunction, vascular hypertrophy, and hypertension in spontaneously hypertensive rats.
INTRODUCTION: We have shown earlier that diacylglycerol (DAG) but not triacylglycerol (TAG) inhibited thrombus formation. The aim of the present study was to investigate the mechanism of this antithrombotic effect of DAG. MATERIALS AND METHODS: Four different diets, the (1) Western-style high-fat diet (HFD) containing 20% lipid and 0.05% cholesterol (w/w), (2) TAG-rich and (3) DAG-rich HFDs containing 20% lipid and 0.05% cholesterol, but all lipid replaced by TAG or DAG oil with very similar fatty acid composition and the (4) Japanese-style low-fat diet (LFD) containing 7% oil but no cholesterol were given to apolipoprotein E and low-density lipoprotein (LDL) receptor double-deficient mice. Atherogenicity was assessed by morphology, mapping the whole aorta and measuring the total area of lipid-stained lesions. Endothelial function was measured by the flow-mediated vasodilation test. Platelet reactivity was assessed from native blood sample by a shear-induced platelet function test (hemostatometry). Serum lipoprotein profile was measured by HPLC. RESULTS: Both the Western-style and the TAG-rich HFDs have accelerated atherosclerosis. In contrast, DAG-rich HFD inhibited the atherosclerotic process to an extent comparable with the Japanese-style LFD. There was no significant difference in platelet and coagulant activity between the studied diet groups. DAG-rich but not the TAG-rich HFD significantly suppressed serum LDL cholesterol level. CONCLUSIONS: The present findings suggest that the mechanism of antithrombotic and anti-atherogenic effect of DAG may involve the protection of the vascular endothelium from injury and lowered serum LDL cholesterol.
Several studies have shown that diacylglycerol (DAG) oil may suppress accumulation of body fat in adults compared to triacylglycerol (TAG) oil. In this study, we investigated the effect of DAG oil as part of dietetic therapy in obese children. The participants were 11 male and female obese children who were under treatment at the outpatient clinic (four boys, seven girls, age: 7-17 years old). Daily-use cooking oil was changed to DAG oil, and the effects on abdominal fat areas, adipocytokines, and serum lipids were investigated. The total and subcutaneous fat areas significantly decreased in the 5th month after ingestion of DAG oil. Leptin was significantly lower than the initial level after ingestion of DAG oil. The ingestion of DAG oil decreased both the abdominal fat area and leptin in obese children, suggesting that DAG oil prevents obesity in children as well as in adults.
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OBJECTIVE: Coronary arteriosclerotic heart disease frequently develops in patients with diabetes. Decreases in [corrected] serum high-density lipoprotein cholesterol (HDL-C) [corrected] concentration and low-density lipoprotein (LDL) particle size, accompanied by hypertriglyceridemia, are associated with the onset of atherosclerosis. We recently reported that hypertriglyceridemia was significantly improved in patients with type 2 diabetes who ingested diacylglycerol (DAG) oil. The effect on variables, including LDL particle size related to lipid metabolism, however, was not examined. The present study investigated the effects on these variables in more detail. METHODS: Patients with type 2 diabetes (n = 24) were assigned to receive DAG oil or triacylglycerol oil, and a 3-mo, single-blind, controlled study was performed. Patients replaced cooking oil in their daily diet with DAG or triacylglycerol oil, and anthropometry and blood sampling were performed at monthly intervals. RESULTS: There were no significant differences in calorie intake or amount of test oil ingested between groups. Waist circumference and serum triacylglycerol concentrations were significantly lower and serum concentrations of high-density lipoprotein cholesterol and apolipoprotein-AI were significantly higher in the DAG oil group than in the triacylglycerol oil group. Plasma plasminogen activator inhibitor-1 concentrations were significantly lower in the DAG oil group. LDL particle size tended to increase in the DAG oil group and was significantly larger in patients who had a small initial LDL particle size (<25.5 nm). There were no significant differences in variables related to glucose metabolism or in serum concentration of free fatty acids or total ketone bodies. CONCLUSIONS: These results indicate that DAG oil may be useful for patients who have type 2 diabetes in the management of obesity and lipid abnormalities.
OBJECTIVE: This study examined the effects of a diacylglycerol (DAG)-containing diet on postprandial energy expenditure and respiratory quotient. METHODS: A randomized, double-blind, crossover, placebo-controlled study with a washout period was performed in 13 healthy male subjects. A 4240-kJ diet containing 30 g of triacylglycerol (TAG) or DAG (TAG meal or DAG meal, containing 34.5% lipids, 52.1% carbohydrates, and 14.1% proteins) was administered after a fasting period of 15 to 16 h. Breath and serum were analyzed for up to 5 h after ingestion of the meal. RESULTS: The amount of change in energy expenditure 3 h after loading with the DAG meal tended to be higher than that after loading with the TAG meal (P < 0.1). Changes in respiratory quotient 2 and 5 h after loading with the DAG meal were significantly lower than those after loading with the TAG meal, suggesting high lipid oxidation activity after the meal. The serum insulin level 0.5 h after loading with the DAG meal was significantly lower than that after loading with the TAG meal. This result suggests that there is a smaller stimulus in the direction of fat storage after loading with the DAG meal. CONCLUSIONS: Compared with the TAG-containing meal, the DAG-containing meal tended to produce a higher postprandial energy expenditure and a significantly lower postprandial respiratory quotient. These results suggest that the DAG-containing meal has high postprandial lipid oxidation activity and a potential effect on high diet-induced thermogenesis.