Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels.

Effect of Vaccinium ashei reade leaf extracts on lipid metabolism in obese OLETF rats.

The effects of a hot water extract and fractional extracts from rabbiteye blueberry (Vaccinium ashei reade) leaves (BBL) on lipid metabolism were studied in obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Feeding the hot water extract and fractional extracts from BBL alleviated hepatic triglyceride accumulation in the rats. Additionally, feeding with the flavonol glycoside (FG) and proanthocyanidin (PA) fractions lowered serum cholesterol levels in the obese rats. The results from measurements of the hepatic enzyme activity indicate that the hypolipidemic effects of the hot water extract and the PA fraction might be attributable to enhanced lipolysis in the liver. The reduced serum levels of C-reactive protein, an inflammatory cytokine, by the chlorogenic acid + rutin fraction and FG fraction might be associated with alleviating the metabolic abnormalities in obese rats. These results indicate that the BBL extracts, and especially FG and PA, exerted hypolipidemic effects on obese OLETF rats and suggest that an infusion of BBL can be useful as a dietary hypolipidemic component.

Hypotriacylglycerolemic and antiobesity properties of a new fermented tea product obtained by tea-rolling processing of third-crop green tea (Camellia sinensis) leaves and loquat (Eriobotrya japonica) leaves.

We manufactured a new fermented tea by tea-rolling processing of third-crop green tea (Camellia sinensis) leaves and loquat (Eriobotrya japonica) leaves. The mixed fermented tea extract inhibited pancreatic lipase activity in vitro, and effectively suppressed postprandial hypertriacylglycerolemia in rats. Rats fed a diet containing 1% freeze-dried fermented tea extract for 4 weeks had a significantly lower liver triacylglycerol concentration and white adipose tissue weight than those fed the control diet lacking fermented tea extract. The activity of fatty acid synthase in hepatic cytosol markedly decreased in the fermented tea extract group as compared to the control group. The serum and liver triacylglycerol- and body fat-lowering effects of the mixed fermented tea extract were strong relative to the level of dietary supplementation. These results suggest that the new fermented tea product exhibited hypotriacylglycerolemic and antiobesity properties through suppression of both liver fatty acid synthesis and postprandial hypertriacylglycerolemia by inhibition of pancreatic lipase.

Taurine Improves Lipid Metabolism and Increases Resistance to Oxidative Stress.

Calorie restriction (CR) by 30-40% decreases morbidity of age-related diseases and prolongs the lifespan of various laboratory animal species. Taurine (2-aminoethanesulfonic acid) is an important nutrient for lipid metabolism as it conjugates bile acids. Here, we investigated how taurine supplementation induces effects similar to the CR beneficial effects. Sprague Dawley rats were fed a diet containing different taurine concentrations (0, 0.5, 1.0, 3.0, 5.0%) to analyze the effects on growth, blood, and hepatic parameters. Rats fed a 5% taurine-supplemented diet showed a significant decrease in visceral fat weight, compared with control rats. Moreover, there were significant decreases in the serum total cholesterol, hepatic cholesterol and triglyceride concentrations in the taurine-supplemented groups compared with the control group in a dose-dependent manner. These results were associated with decreased mRNA expression of fatty acid synthase, and increased mRNA expression of carnitine palmitoyltransferase 1α. C57BL/6 mice were fed a 5.0% taurine-supplemented diet, and their response to 3-nitropropionic acid-induced oxidative stress was analyzed. The rate of weight loss due to oxidative stress decreased and the survival rate significantly increased in the taurine-supplemented groups compared with the control group. Finally, cells were treated with 100 µM taurine and their resistance to UV-induced oxidative stress was analyzed. We found that the p53-Chk1 pathway was less activated in taurine-treated cells compared with control cells. Furthermore, damage to cells evaluated by oxidative stress indicators revealed a reduction in oxidative damage with taurine treatment. These findings suggest that taurine partially acts as a CR mimetic.

Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat.

The Shumiya cataract rat (SCR) is a hereditary cataractous strain. It is thought that the continuous occurrence of poorly differentiated epithelial cells at the bow area of the lens forms the pathophysiological basis for cataract formation in SCRs. In this study, we attempted to identify the genes associated with cataract formation in SCRs by positional cloning. Genetic linkage analysis revealed the presence of a major cataract locus on chromosome 20 as well as a locus on chromosome 15 that partially suppressed cataract onset. Hypomorphic mutations were identified in genes for lanosterol synthase (Lss) on chromosome 20 and farnesyl diphosphate farnesyl transferase 1 (Fdft1) on chromosome 15, both of which function in the cholesterol biosynthesis pathway. A null mutation for Lss was also identified. Cataract onset was associated with the specific combination of Lss and Fdft1 mutant alleles that decreased cholesterol levels in cataractous lenses to about 57% of normal. Thus, cholesterol insufficiency may underlie the deficient proliferation of lens epithelial cells in SCRs, which results in the loss of homeostatic epithelial cell control of the underlying fiber cells and eventually leads to cataractogenesis. These findings may have some relevance to other types of cataracts, inborn defects of cholesterol synthesis, and the effects of cholesterol-lowering medication.

Hypoglycemic activity of Eriobotrya japonica seeds in type 2 diabetic rats and mice.

The hypoglycemic effects of Eriobotrya japonica seeds were investigated in type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and KK-A(y) mice. The rats and mice were fed on a diet containing 10% powdered Eriobotrya japonica seeds with the coat intact for 4 months. Although the blood glucose concentration in the OLETF rats fed on the control diet without Eriobotrya japonica seeds was increased with time, the concentration in the OLETF rats fed on the diet with Eriobotrya japonica seeds was consistently low throughout the experimental period and was comparable to the level in Long-Evans Tokushima Otsuka (LETO) rats which are normal non-diabetic rats. Serum insulin was significantly lower in the OLETF rats fed on the Eriobotrya japonica seed diet than in those fed on the control diet at the termination of the experimental period. Eriobotrya japonica seeds suppressed the increment of blood glucose for 4 months and also effectively improved the glucose tolerance in the KK-A(y) mice, these actions being mainly exerted by the ethanol extract of the seeds. These results suggest that Eriobotrya japonica seeds had a hypoglycemic property and the effect is attributable to the components extracted by ethanol.

Genetically modified rapeseed oil containing cis-9,trans-11,cis-13-octadecatrienoic acid affects body fat mass and lipid metabolism in mice.

Punicic acid, one of the conjugated linolenic acid (CLN) isomers, exerts a body-fat reducing effect. Although punicic acid is found in pomegranate and Tricosanthes kirilowii seeds, the amount of this fatty acid is very low in nature. The goal of this study was to produce a transgenic oil containing punicic acid. A cDNA encoding conjugase that converts linoleic acid to punicic acid was isolated from T. kirilowii, and the plant expression vector, pKN-TkFac, was generated. The pKN-TkFac was introduced into Brassica napus by Agrobacterium-mediated transformation. As a result, a genetically modified rapeseed oil (GMRO) containing punicic acid was obtained, although its proportion to the total fatty acids was very low (approximately 2.5%). The effects of feeding GMRO in ICR CD-1 male mice were then examined. Wild-type rapeseed (B. napus) oil (RSO) containing no CLN was used as a control oil. For reference oils, RSO-based blended oils were prepared by mixing with different levels of pomegranate oil (PO), either 2.5% (RSO + PO) or 5.0% (RSO + 2PO) punicic acid. Mice were fed purified diets containing 10% of either RSO, RSO + PO, RSO + 2PO, or GMRO for 4 weeks, and dietary PO dose-dependently reduced perirenal adipose tissue weight with a significant difference between the RSO group and the RSO + 2PO group. GMRO, as compared to RSO, lowered the adipose tissue weight to the levels observed with RSO + 2PO. The liver triglyceride level of the RSO + 2PO and GMRO groups but not that of the RSO + PO group was lower than that of the RSO group. The RSO + 2PO and GMRO groups, but not the RSO + PO group, had increased carnitine-palmitoyltransferase activity in the liver and brown adipose tissue. These results showed that dietary GMRO, even at a dietary punicic acid level as low as 0.25 wt % of diet, reduced body fat mass and altered liver lipid metabolism in mice and was more effective than an equal amount of punicic acid from PO.

Lymphatic absorption and deposition of various plant sterols in stroke-prone spontaneously hypertensive rats, a strain having a mutation in ATP binding cassette transporter G5.

ATP binding cassette transporter G5 (ABCG5) and ATP binding cassette transporter G8 (ABCG8) have been suggested to transport absorbed plant sterols and cholesterol from enterocytes to the intestinal lumen and from hepatocytes to bile. It has been thought that mutations of ABCG5 or ABCG8 cause the deposition of plant sterols in the body. In the present study, lymphatic absorption of various plant sterols and their deposition in various tissues was investigated in stroke-prone spontaneously hypertensive rats (SHRSP), having a mutation in Abcg5 and depositing plant sterols in the body. The order of lymphatic 24-h recovery of plant sterols was as follows: campesterol > sitosterol > brassicasterol > stigmasterol = sitostanol. When SHRSP were fed a diet containing one of the plant sterols, the depositions of campesterol and sitosterol were comparatively higher than those of brassicasterol, stigmasterol and sitostanol. Highly positive correlations were obtained between lymphatic recovery of plant sterols and their levels in plasma, liver, adipose tissue and heart. The tendency of differential absorption of plant sterols to the lymph in SHRSP was similar to that in normal Wistar rats previously reported by us (Hamada et al. Lipids 41:551-556, 2006). These observations suggest that differential absorption of various plant sterols is kept in SHRSP in spite of a mutation in Abcg5.

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.

Effects of dietary oyster extract on lipid metabolism, blood pressure, and blood glucose in SD rats, hypertensive rats, and diabetic rats.

Oyster extract was prepared by hydrolysis of oyster protein with proteases, Aloase (a protease from Bacillus subtilis), and Pancitase (a protease from Aspergillus oryzae). Rats were fed a diet containing 20% casein (the control diet) or 15% casein and 5% oyster extract (the oyster extract diet) as the protein source. The oyster extract diet exerted a significant reduction in serum cholesterol and liver triglyceride concentrations as compared with the control diet in Sprague-Dawley (SD) rats fed cholesterol-supplemented diets for 4 weeks. The activities of cytosolic fatty acid synthase and glucose-6-phosphate dehydrogenase were significantly lower in the oyster extract group than in the control group in the liver of SD rats. Hepatic cholesterol and triglyceride concentrations were significantly lower in spontaneously hypertensive (SH) rats and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, type 2 diabetic rats, fed the oyster extract diet, for 4 weeks and 4 months respectively, than in those fed the control diet in the cholesterol-free diet. Blood pressure was significantly lower in the oyster extract group than in the control group at the 2nd and 4th weeks after the beginning of feeding experimental diets in SH rats. These results suggest that oyster extract prepared by hydrolysis of oyster induces triglyceride-lowering activity in the liver through a decrease in hepatic lipogenesis in SD rats, and that it exerts the antihypertensive effect in SH rats.