Biomedical subjects

Ikuo Ikeda

Publications and source records attributed to Ikuo Ikeda.

7 recordsLinked to original sources

PubMed2003

The rat STSL locus: characterization, chromosomal assignment, and genetic variations in sitosterolemic hypertensive rats.

BACKGROUND: Elevated plant sterol accumulation has been reported in the spontaneously hypertensive rat (SHR), the stroke-prone spontaneously hypertensive rat (SHRSP) and the Wistar-Kyoto (WKY) rat. Additionally, a blood pressure quantitative trait locus (QTL) has been mapped to rat chromosome 6 in a New Zealand genetically hypertensive rat strain (GH rat). ABCG5 and ABCG8 (encoding sterolin-1 and sterolin-2 respectively) have been shown to be responsible for causing sitosterolemia in humans. These genes are organized in a head-to-head configuration at the STSL locus on human chromosome 2p21. METHODS: To investigate whether mutations in Abcg5 or Abcg8 exist in SHR, SHRSP, WKY and GH rats, we initiated a systematic search for the genetic variation in coding and non-coding region of Abcg5 and Abcg8 genes in these strains. We isolated the rat cDNAs for these genes and characterized the genomic structure and tissue expression patterns, using standard molecular biology techniques and FISH for chromosomal assignments. RESULTS: Both rat Abcg5 and Abcg8 genes map to chromosome band 6q12. These genes span ~40 kb and contain 13 exons and 12 introns each, in a pattern identical to that of the STSL loci in mouse and man. Both Abcg5 and Abcg8 were expressed only in liver and intestine. Analyses of DNA from SHR, SHRSP, GH, WKY, Wistar, Wistar King A (WKA) and Brown Norway (BN) rat strains revealed a homozygous G to T substitution at nucleotide 1754, resulting in the coding change Gly583Cys in sterolin-1 only in rats that are both sitosterolemic and hypertensive (SHR, SHRSP and WKY). CONCLUSIONS: The rat STSL locus maps to chromosome 6q12. A non-synonymous mutation in Abcg5, Gly583Cys, results in sitosterolemia in rat strains that are also hypertensive (WKY, SHR and SHRSP). Those rat strains that are hypertensive, but not sitosterolemic (e.g. GH rat) do not have mutations in Abcg5 or Abcg8. This mutation allows for expression and apparent apical targeting of Abcg5 protein in the intestine. These rat strains may therefore allow us to study the pathophysiological mechanisms involved in the human disease of sitosterolemia.

Animals↗

PubMed2003

Decrease in plasma low-density lipoprotein cholesterol, apolipoprotein B, cholesteryl ester transfer protein, and oxidized low-density lipoprotein by plant stanol ester-containing spread: a randomized, placebo-controlled trial.

OBJECTIVE: The ester of plant stanols significantly reduces plasma levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in Western people. Effects of plant stanol ester-containing spread on plasma levels of TC, LDL-C, and apolipoprotein B (apoB) were studied in a randomized, placebo-controlled trial in Japanese subjects whose diet is low in fat and cholesterol. The effects of plant stanol ester on plasma levels of arteriosclerosis-promoting factors, namely remnants of triacylglycerol (TG)-rich lipoproteins, cholesteryl ester transfer protein (CETP), and oxidized LDL (Ox-LDL), were also studied. The assessment of safety was also made. METHODS: One hundred and five healthy volunteers were assigned randomly to one of three groups: placebo spread (n = 35), 2 g/d of plant stanol (3.4 g of stanol ester; n = 34), and 3 g/d of plant stanol (5.1 g of stanol ester; n = 36). Plasma levels of lipids were measured at start of the study, at 2 and 4 wk (end of trial), and at 8 wk (+4 wk). Plasma apoproteins, cholesterol in remnant-like particles which are equivalent to remnants of TG-rich lipoproteins (RLP-C), CETP mass, and Ox-LDL were measured at the beginning and the end of the trial. Plasma levels of plant steroids and fat-soluble vitamins were also measured for the assessment of safety. RESULTS: Background and dietary composition did not differ among groups. Plasma levels of TC, LDL-C, apoB, apoE, CETP mass, and Ox-LDL were reduced significantly by 6.5%, 9.6%, 8.3%, 4.5%, 6.1%, and 20%, respectively, in the 2 g/d plant stanol group. Plasma levels of TC, LDL-C, apoB, CETP mass, and Ox-LDL were decreased significantly by 5.5%, 7.3%, 5.6%, 3.3%, and 19%, respectively, in the 3 g/d plant stanol group. Plasma levels of plant stanols, plant sterols, retinol, beta-carotene, and alpha-tocopherol did not change in any group, but levels of campestanol increased and alpha-tocopherol decreased slightly in the sitostanol groups. CONCLUSION: Plasma levels of TC and LDL-C were significantly reduced by the plant stanol ester-containing spread. The smaller reduction than in Western studies and the lack of dose dependency in this study might be due to the different basal diets. We concluded that plant stanol ester-containing spread is efficacious in reducing plasma LDL-C, apoB, CETP, and Ox-LDL and that 2 g/d plant stanol is adequate for Japanese people. No significant side effects were observed in any group.

Apolipoproteins B↗

PubMed2003

Effects of feeding oyster, Crassostrea gigas, on serum and liver lipid levels in rats.

The effects of feeding dietary and defatted oyster meat on lipid metabolism were investigated in rats by comparing measurements with those of casein and soybean protein. In the first experiment, male rats were fed 0.1% and 1% cholesterol-supplemented diets containing casein, oyster or soybean protein under the same dietary level of protein (20%). The concentrations of serum and liver cholesterol in the oyster group were significantly lower than those in the casein group for both the 0.1% and 1% cholesterol-supplemented diets. The cholesterol-lowering effect of oyster meat was more predominant than that of soybean protein. Feeding oyster meat significantly decreased the serum triglyceride concentration as compared to feeding casein for the 0.1% cholesterol-supplemented diets, and it reduced hepatic triglyceride concentration in both groups fed the 0.1% and 1% cholesterol-supplemented diets. The excretion of fecal total steroids was higher in the rats fed oyster meat than those fed casein or soybean protein for both the 0.1% and 1% cholesterol-supplemented diets. In the second experiment, the effects of defatted oyster on lipid metabolism were compared with casein and soybean protein in diets supplemented with cholesterol. The serum cholesterol concentration in the defatted oyster group was comparable to that in the other two groups, but the ratio of high-density lipoprotein-cholesterol to total cholesterol was higher in the defatted oyster group. The feeding of defatted oyster induced a lower liver cholesterol concentration as compared to casein and soybean protein. Serum and liver triglyceride levels were lower in the defatted oyster group than in the casein group. Defatted oyster accelerated the fecal excretion of both neutral and acidic steroids as compared to casein. Our results suggest that the feeding of oysters exerts a more potent hypolipidemic activity than soybean protein, and the effect may be ascribed to both lipid and non-lipid fractions in oyster.

Animals↗

PubMed2002

Cholesterol esterase accelerates intestinal cholesterol absorption.

Mechanisms of acceleration of cholesterol absorption by cholesterol esterase were investigated in various experimental conditions. Lymphatic recovery of cholesterol intubated as a micellar solution containing phosphatidylcholine (PC) into the duodenum was enhanced by the co-administration of cholesterol esterase in rats drained of bile and pancreatic juice. However, no accelerated incorporation was observed when cholesterol was solubilized in PC-depleted micelles. Cholesterol esterase dose-dependently accelerated the incorporation of cholesterol into differentiated Caco-2 cells, only when cholesterol was solubilized in PC-containing micelles. The accelerated incorporation of cholesterol into Caco-2 cells by cholesterol esterase disappeared when the enzyme was preincubated with a suicide inhibitor of cholesterol esterase. Cholesterol esterase has an activity as phospholipase A(2). When 10% of PC in bile salt micelles was replaced by lysophosphatidylcholine (lysoPC), the incorporation of cholesterol into Caco-2 cells was significantly accelerated. Cholesterol esterase enhanced the incorporation of micellar cholesterol into brush border membranes prepared from the rat jejunum. The addition of cholesterol esterase to bile salt micelles accelerated the release of micellar cholesterol in a dose-dependent manner, only when the micelles contained PC. These observations strongly suggest that cholesterol esterase hydrolyzes PC in bile salt micelles and thereby, accelerating the release of cholesterol from bile salt micelles. This may be a major cause of the acceleration of cholesterol absorption by cholesterol esterase.

Animals↗

PubMed2002

Effect of sesaminol on plasma and tissue alpha-tocopherol and alpha-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 alpha- and gamma-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 Experiment 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% alpha-tocopherol, 22% alpha-tocotrienol, and 34% gamma-tocotrienol, alpha-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 alpha-tocotrienol and no gamma-tocotrienol at all. Addition of sesaminol to the T-mix resulted in significantly higher plasma, liver, and kidney alpha-tocopherol concentrations compared to values for T-mix alone. Further, T-mix with sesaminol resulted in significantly higher alpha-tocotrienol concentrations in kidney, although the concentration was very low. In Experiment 2, we examined whether sesaminol caused enhanced absorption of alpha-tocopherol and alpha-tocotrienol in a dosage regimen supplying T-mix and sesaminol on alternating days and observed significantly higher levels of alpha-tocopherol and alpha-tocotrienol in rats fed sesaminol, even without simultaneous intake, compared to those in rats without sesaminol. In Experiment 3, alpha-tocopherol was supplied to the stomach with and without sesaminol, and alpha-tocopherol concentrations in the lymph fluid were measured. a-Tocopherol concentrations were not different between groups. These results indicated that sesaminol produced markedly higher alpha-tocopherol concentrations in plasma and tissue and significantly greater alpha-tocotrienol concentrations in kidney and various other tissues, but the concentrations of alpha-tocotrienol were extremely low compared to those of a-tocopherol (Exps. 1 and 2). However, the sesaminol-induced increases of a-tocopherol and a-tocotrienol concentrations in plasma and tissue were not caused by their enhanced absorption since sesaminol did not enhance their absorption.

Animals↗

PubMed2002

Tocotrienol levels in various tissues of Sprague-Dawley rats after intragastric administration of tocotrienols.

A tocotrienol (T3) mixture was intragastricaly administered to Sprague-Dawley rats, and the T3 levels in various tissues were measured 0, 4, 8 and 24 hr after the administration. In blood clots, brain, thymus, testes, vice-testes and muscles, T3 homologues were not detected at all. In epididymal adipose, renal adipose, subcutaneous adipose and brown adipose tissues and in the heart, the T3 levels were maintained or increased for 24 hr after the administration. In the serum, liver, mesenteric lymph node, spleen and lungs, the T3 levels were highest 8 hr after the T3 administration. These results suggest that the distribution and metabolism of T3 in the rat vary considerably among different tissues.

Animals↗

PubMed2002

Lymphatic transport of dietary cholesterol oxidation products, cholesterol and triacylglycerols in rats.

Rats were fed on a diet containing 0.5% cholesterol oxidation products (oxysterols) or 0.5% cholesterol for 30 min, and their lymph was collected for 7 h. The amount of each of the individual oxysterols absorbed in the lymph depended on the ingested amounts, but the recovery was the highest for 5alpha,6alpha-epoxycholesterol (10.5%), this being followed by 7-ketocholesterol (5.8%), cholestanetriol (5.2%), 7beta-hydroxycholesterol (4.8%), 7alpha-hydroxycholesterol (3.4%), 5beta,6beta-epoxycholesterol (2.2%), and 25-hydroxycholesterol (1.8%). A diet enriched with oxysterol, but not cholesterol, resulted in increased transport of triacylglycerols in the lymph. These results suggest that the absorption rate of oxysterols depends on the type, and indicate that the effect of dietary oxysterols on the lymphatic transport of triacylglycerols differs from that of dietary cholesterol. It therefore remains to be determined which oxysterol was responsible for the triacyglycerol transport.

Animals↗