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.

Dietary soybean peptides containing a low-molecular fraction can lower serum and liver triglyceride levels in rats.

We investigated the effects of dietary soybean peptides, particularly low-molecular-weight peptides, on serum and hepatic concentrations of lipids in rats. Soybean protein isolate (SPI) was digested with protease to produce low-molecular-weight peptides (LD) or a mixture of high- and low-molecular-weight peptides (HLD). Rats were fed diets containing 20% casein, SPI, LD or HLD as a nitrogen source, with or without 0.5% cholesterol, for 2 wk. Next, rats were fed cholesterol-free diets containing 0%, 5%, 10%, or 20% LD at the expense of casein for 2 wk. Serum triglyceride levels were the lowest in the LD group, and liver triglyceride levels were significantly lower in rats fed SPI and LD/HLD diets than in those fed casein diets, both in the presence and absence of dietary cholesterol. In addition, dietary LD significantly lowered serum and liver triglyceride levels in a dose-dependent manner. These results suggest that low-molecular-weight soybean peptides have a potent hypotriglyceridemic effect and may be beneficial for improving lipid metabolism.

Effect of dietary blueberry (Vaccinium ashei Reade) leaves on serum and hepatic lipid levels in rats.

The serum and liver lipid-lowering effects of dietary freeze-dried blueberry leaf powder (BL) and its hydrothermal extract (BLHE) were examined in rats fed diets with or without cholesterol supplementation. Administration of 1% and 3% BL had no adverse effects on food intake or growth; however, relative liver weights were reduced in rats fed diets with and without dietary cholesterol. In the absence of dietary cholesterol, a dose-dependent reduction was evident. The effects of dietary BL on the concentration of serum lipids were marginal; however, the effects on liver triacylglycerol (TG) and cholesterol levels were apparently dose-dependent when the animals were fed diets free of cholesterol. Further, BL significantly attenuated dietary cholesterol-dependent accumulation of hepatic cholesterol, but not of TG. Hydrothermal treatment studies suggested that the active component of BL in terms of its liver lipid-lowering activity is relatively stable at high temperatures. Histopathological analysis of hepatic tissues revealed that BL administration suppresses fatty infiltrations induced by an AIN 76-based high-sucrose diet. The results of this study suggest that some of the active components of BL extracts, which are incorporated into the liver, prevent fatty liver in rats. These results provide further support for the investigation of dietary BL and derivatives thereof as functional human foods.

Mechanisms underlying decreased hepatic triacylglycerol and cholesterol by dietary bitter melon extract in the rat.

In these studies, we focused on finding the mechanism(s) underlying the bitter melon (Momordica charantia L.) methanol fraction (MF)-dependent reduction in the concentration of hepatic triacylglycerol (TAG) and cholesterol in the rat. Rats were fed diets containing low (5 %) fat for 2 weeks (experiment 1), or low (5 %) and high (15 %) fat for a longer period of 8 weeks (experiment 2). MF was supplemented at 1 % level in both experiments. After feeding, rats were sacrificed, and their livers were prepared as slices and hepatocytes, followed by incubation with [1(2)-¹4C] acetate or [1-¹4C] oleic acid (18:1 n-6). Under these conditions, we found that rats fed diets containing MF, as compared to those without MF, showed: (1) no adverse effects on food intake and growth, (2) a decreased hepatic TAG and total cholesterol, irrespective of the difference in dietary fat level or feeding period, and (3) a decreased incorporation of [1(2)-(¹4C] acetate and [1-¹4C] oleic acid into TAG of liver slices and hepatocytes. MF-supplemented rats also showed no altered incorporation of labeled acetate into cholesterol and cholesterol ester, an increased fecal excretion of neutral steroids, but not of acidic steroids, and an enhanced mRNA abundance of carnitine palmitoylacyltransferase I, which is the rate-limiting enzyme for fatty acid oxidation. These results suggest that dietary MF decreases hepatic TAG synthesis while enhancing fatty acid oxidation, thereby reducing the concentration of hepatic TAG. The liver cholesterol-lowering effect of MF, however, is probably mediated through an increased fecal excretion of neutral steroids, without an effect on cholesterogenesis.

Dietary taurine reduces hepatic secretion of cholesteryl ester and enhances fatty acid oxidation in rats fed a high-cholesterol diet.

We investigated the fate of exogenous fatty acid in connection with decreased hepatic accumulation and secretion of cholesteryl esters in rats fed diets containing taurine. Providing taurine as 5% of the diet for 14 d significantly decreased concentrations of cholesterol, especially cholesteryl esters in both serum and liver. Ketone body production and incorporation of exogenous [1-(14)C]oleate into ketone bodies in liver perfusate were consistently higher during a 4-h perfusion period in taurine-fed rats than in control rats. The elevation was accompanied by increased activity of liver mitochondrial carnitine palmitoyltransferase, a rate-limiting enzyme for fatty acid oxidation. Dietary taurine significantly reduced hepatic secretion of cholesteryl ester and decreased incorporation of exogenous oleic acid substrate into this lipid molecule. Further, the extent of reduction in hepatic secretion of cholesteryl ester was closely related to its diminished accumulation in the liver. The conversion pattern of exogenous [1-(14)C]oleic acid substrate suggested a decreased esterification-to-oxidation ratio in the taurine group compared with the control. These results suggest that taurine-induced reduction in hepatic accumulation of cholesteryl ester was associated with reduced hepatic secretion of this lipid molecule, and was inversely related to enhanced ketone body production and fatty acid oxidation.

Prevention of neointima formation by taurine ingestion after carotid balloon injury.

The sulfur-containing amino acid, taurine, has been shown to ameliorate the vascular disorders. We examined the effects of taurine ingestion on intimal thickening following balloon injury. Balloon injury was induced in the left common carotid artery of Wistar rats. Taurine (3% (w/v)) was mixed in the drinking water from 2 days prior to, until 14 days after the induction of balloon injury. The ratio of intima-to-media was significantly reduced by 26% in the taurine-treated rats at 14 days after the induction of injury, which was associated with reduced proliferation of the vascular smooth muscle cells (SMCs) in both the media and the intima. Attenuation of arterial superoxide production by taurine ingestion was evident from the results of both the lucigenin chemiluminescence method and in situ detection by dihydroethidium (DHE) staining. Moreover, LPS-stimulated TNF-alpha production in the blood cells was decreased in the taurine-treated rats. The results of the study showed that taurine suppresses neointimal formation in balloon-injured arteries, associated with reduced proliferation of the vascular SMCs, which is attributable to the anti-oxidative effects of taurine. In addition, the anti-inflammatory effects of taurine chloramine produced by neutrophils may be related to reduction in SMC proliferation in part.

Effects of dietary soybean peptides on hepatic production of ketone bodies and secretion of triglyceride by perfused rat liver.

Soybean protein isolate (SPI) was digested with protease to produce a peptides containing the low-molecular fraction (LD3) or a mixture of high- and low-molecular fractions (HD1). Rats were fed a diets containing SPI, LD3, or HD1 at a protein level equivalent to the 20% casein diet for 4 weeks. The serum triglyceride concentration was lower in rats fed SPI, LD3, and HD1 diets than in rats fed the casein diet, and the differences were significant for the cholesterol-enriched diet. The value for the LD3 group was the lowest among all groups for both the cholesterol-free and -enriched diets. The level of triglyceride in the post-perfused liver was significantly lower in the LD3 and HD1 groups and the SPI group than in the casein group irrespective of the presence of cholesterol in the diet. In the cholesterol-free diet, LD3 feeding as compared to casein feeding caused a reduction in triglyceride secretion from the liver to perfusate and an increment of hepatic ketone body production. The addition of cholesterol to the diets somewhat attenuated these effects of LD3. These results suggest that the low-molecular fraction in soybean peptides causes triglyceride-lowering activity through a reduction in triglyceride secretion from the liver to the blood circulation and the stimulation of fatty acid oxidation in the liver. There is a possibility that soybean peptides modulate triglyceride metabolism by changes in the hepatic contribution.

Dietary 5-campestenone (campest-5-en-3-one) enhances fatty acid oxidation in perfused rat liver.

The effect of dietary 5-campestenone (campest-5-en-3-one), a chemical modification product of a naturally-occurring plant sterol, campesterol, on lipid metabolism was examined using a rat liver perfusion system. Male Sprague-Dawley rats weighing about 140 g were fed a diet supplemented with or without 0.2% 5-campestenone for 14 d. 5-Campestenone feeding resulted in a marked reduction in the concentrations of serum lipids, such as triacylglycerol (TG), cholesterol, phospholipid, and free fatty acid, without influencing food intake or growth. Then, isolated livers from both groups were perfused for 4 h in the presence of an exogenous linoelaidic acid substrate. Dietary 5-campestenone markedly elevated hepatic ketone body production, while cumulative secretions of TG, cholesterol, and phospholipid by the livers of rats fed 5-campestenone were all significantly lowered as compared to those fed without the compound: the extent of the reduction was more prominent in the secretion of TG than other lipid components. In addition, the reduction of TG secretion was concomitantly accompanied by the reduced incorporation of both exogenous and endogenous fatty acids into this lipid molecule. These results suggest that dietary 5-campestenone exerts its hypotriglyceridemic effect, at least, in part through an enhanced metabolism of endogenous and exogenous fatty acids to oxidation at the expense of esterification in rat liver.

The effects of bitter melon (Momordica charantia) extracts on serum and liver lipid parameters in hamsters fed cholesterol-free and cholesterol-enriched diets.

The hypolipidemic effect of dietary methanol fraction (BMMF) extracted from bitter melon (Koimidori variety), at the levels of 0.5% and 1.0%, was examined in male golden Syrian hamsters fed diets supplemented with and without cholesterol. The feeding of BMMF at 0.5% and 1.0% levels in the diets for 4 wk tended to reduce food intake and growth, although there was no difference in food efficiency (weight gain/food intake). An effect of dietary BMMF on serum triglyceride was not seen in hamsters fed diets free of cholesterol, while hypertriglyceridemia induced by dietary cholesterol was significantly lowered in a dose-dependent manner in those fed diets containing the BMMF Serum total cholesterol concentration also tended to decrease in a dose-dependent manner following feeding of increasing amounts of BMMF in the presence and absence of cholesterol in the diet. The effects of dietary BMMF on liver triglyceride and total cholesterol levels were marginal, although dietary cholesterol caused a marked accumulation of these lipid molecules in the liver. These results suggest that the BMMF contains some components that could ameliorate lipid disorders such as hyperlipidemia.

The effects of bitter melon (Momordica charantia) on serum and liver triglyceride levels in rats.

Effects of three different varieties (Koimidori, Powerful-Reishi, and Hyakunari) of bitter melon (Momordica charantia) and those of methanol fraction extract of Koimidori variety on serum and liver triglycerides were studied in rats. Feeding of diets containing either bitter melon or various fractions isolated by organic solvents caused no adverse effects on food intake or growth of rats. When the effect of three different varieties of bitter melon was compared, the Koimidori variety was found to be the most effective in lowering hepatic triglyceride levels as compared to the other two varieties, suggesting a variety-dependent difference in their activity. Furthermore, the active component(s) responsible for the liver triglyceride lowering activity of Koimidori variety was assumed to be concentrated in the methanol fraction, but not in other fractions such as the n-hexane, the acetone, or the residual fraction. The triglyceride lowering activity was furthermore confirmed by the dose-dependent reduction of hepatic triglyceride, resulting the lowest level in rats fed 3.0% supplementation. In these experiments, the effects on serum lipids were marginal. The results of the present and previous studies clearly show that bitter melon, especially Koimidori variety, exhibits a potent liver triglyceride-lowering activity.

Purification and characterization of laminaran hydrolases from Trichoderma viride.

At least three extracellular laminaran hydrolases which hydrolyzed laminaran (beta-1,3:1,6-glucan) from Eisenia bicyclis were secreted in wheat bran solid medium by Trichoderma viride U-1. These three enzymes, lam AI, AII, and B, were purified to electrophoretic homogeneity. Their molecular masses were estimated to be 70.1, 70.4, and 45.0 kDa for lam AI, AII, and B, respectively, by SDS-PAGE. Whereas both lam AI and AII could hydrolyze laminarin from Laminaria digitata, lam AII showed higher activity against Laminaria laminarin rather than Eisenia laminaran. On the other hand, lam B preferentially hydrolyzed pustulan, a beta-1,6-glucan. Laminarioligosaccharide was hydrolyzed by lam AI and AII but not B, whereas gentiooligosaccharide was hydrolyzed by only lam B. It showed that lam AI and AII were specific for beta-1,3-linkages, but lam B was specific for beta-1,6-linkages. These results indicated that T. viride U-1 has a multiple glucanolytic enzyme system.

Effect of taurine on cholesterol metabolism in hamsters: up-regulation of low density lipoprotein (LDL) receptor by taurine.

The effects of taurine on hepatic cholesterol metabolism were investigated in hamsters fed a high-fat diet or normal chow. Two weeks-treatment of taurine at 1% in drinking water prevented high-fat diet-induced increase in cholesterol levels of serum and liver. The decrease in serum cholesterol by taurine was due to decrease in non-HDL cholesterols. A similar tendency was noted in serum and liver cholesterol levels of hamsters fed a normal diet. In hamsters fed a high-fat diet, taurine prevented elevation in hepatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and increased the activity of cholesterol 7alpha-hydroxylase. Taurine also increased cholesterol 7alpha-hydroxylase activity in hamsters fed normal chow. Studies on liver membranes revealed that taurine increased 125I-labeled LDL binding by 52% and 58% in hamsters fed either a normal chow or high-fat diet, respectively. Furthermore, LDL kinetic analysis showed that taurine intake resulted in significant faster plasma LDL fractional catabolic rates (FCR). These results suggest that taurine elevates hepatic LDL receptor and thereby decreases serum cholesterol levels, an event which may be the result of hepatic cholesterol depletion as a consequence of increased bile acid synthesis via enhancement of cholesterol 7alpha-hydroxylase activity. Thus, up-regulation of the LDL receptor and subsequent increase in receptor- mediated LDL turnover may be a key event in the cholesterol-lowering effects of taurine in hamsters.

Combined effects of dietary conjugated linoleic acid and sesamin triacylglycerol and ketone body production in rat liver.

The effects of a combination of dietary conjugated linoleic acid (CLA) supplemented with sesamin on hepatic ketogenesis and triacylglycerol secretion were compared using the livers of rats fed diets containing 1% CLA or linoleic acid (LA) in combination with 0.2% sesamin for 14 d, respectively. The feeding of CLA, as compared to LA, caused a significant reduction in the weight of perirenal adipose tissue but not that of epididymal adipose tissue, and affected neither growth parameters nor hepatic lipid concentration. Hepatic production of ketone bodies was consistently higher in rats fed CLA than in those fed LA, while triacylglycerol secretion was reversed. No significant difference was noted in the hepatic secretion of cholesterol among the groups. Although there was no effect of the dietary combination of CLA with sesamin on adipose tissue weight, hepatic lipid parameters and ketone body production were observed: i.e., triacylglycerol secretion tended to be reduced. These results suggest that the dietary combination of CLA with sesamin may be an effective approach for lowering serum triacylglycerol levels. The decreased hepatic secretion of triacylglycerol is, in part, due to enhanced fatty acid oxidation in the liver.