Tissue taurine content and conjugated bile acid composition of rhesus monkey infants fed a human infant soy-protein formula with or without taurine supplementation for 3 months

The concentrations of taurine in a number of brain regions and in other tissues of rhesus morkeys fed a taurine-free human infant formula for 3 months are substantially lower than in similar monkeys fed the same formula supplemented with taurine. Activities of enzymes involved in taurine biosynthesis were not different in the two groups except for liver cysteinesulfinic acid decarboxylase, which was greater in the monkeys fed formula alone. There was no difference in the biliary bile acid composition, but the proportion of bile acids conjugated with taurine was significantly greater in the monkeys fed formula supplemented with taurine. These results indicate that the effects of a taurine-deficient diet on infant primates are widespread.     

Taurine deficiency in the kitten subcellular distribution of taurine and [35S]taurine in brain

Taurine concentration decreases rapidly in the tissues and physiological fluids of kittens fed a diet of partially purified casein which lacks taurine. We have studied the subcellular distribution in cerebrum of taurine and [³⁵S]taurine administered intravenously to these animals. The taurine concentration of all the fractions isolated from the cerebrum of taurine-deficient kittens was approximately sevenfold less than that observed in the fractions of cerebrum isolated from control kittens. The [³⁵S]taurine was approximately twofold greater in all the brain fractions isolated from the taurine-deficient kittens compared with those isolated from the control kittens. The percent distributions of taurine and [³⁵S]taurine in the fractions isolated from the cerebrum of control and deficient kittens were identical. Thus, in the face of a severe diet-induced deficiency of taurine in kitten brain, there appears to be no conservation of taurine by any particular subcellular pool of taurine. These studies provide no evidence for differences in compartmentation of taurine in cerebrum of taurine-deficient kittens compared with control kittens.     

Increase of bile acids synthesis and excretion caused by taurine administration prevents the ovariectomy-induced increase in cholesterol concentrations in the serum low-density lipoprotein fraction of Wistar rats

We examined the effect of dietary taurine on the concentrations of serum cholesterol and apolipoprotein in lipoprotein fractions of Six-month-old ovariectomized, which were used as a model of hypercholesterolemia in postmenopausal woman, or sham operated rats. Taurine significantly reduced the serum total and low-density lipoprotein cholesterol concentrations only in the ovariectomized rats. In contrast, taurine significantly lowered the serum apolipoprotein B concentration and serum very low-density lipoprotein-apolipoprotein E concentration only in the sham operated rats. The serum total and high density lipoprotein-apolipoprotein E concentrations were significantly lower in the rats fed taurine than in those fed the control diet regardless of whether they had undergone ovariectomy. The esterified cholesterol level in the liver was significantly lower and the level of hepatic cholesterol 7 alpha-hydroxylase activity was significantly higher in the rats fed taurine than in those fed the control diet. The total bile acids concentration in the feces and intestinal contents of rats fed taurine were significantly higher than those in rats fed the control diet regardless of whether they had undergone ovariectomy. In the sham-rats, taurine accelerated bile acid synthesis and excretion, thereby increasing cholesterol consumption. The increased cholesterol consumption might be compensated by accelerating cholesterol synthesis and/or reducing the synthesis and release of very low-density lipoprotein from the liver. But in the ovariectomized rats, although taurine also accelerated bile acid synthesis and excretion, cholesterol demand might be compensated by excess cholesterol in the blood.     

Hypolipidemic action of taurine in rats.

The effect of taurine on the serum and liver cholesterol and triglyceride levels was studied in rats fed cholesterol plus cholic acid. Four groups of 4 weeks old rats were fed control diet, hypercholesterolemic diet (HCD), HCD + 1% taurine or HCD + 2% taurine for 8 weeks. Addition of taurine in HCD diet showed a significant reduction not only in serum total cholesterol and triglyceride levels but also in liver total cholesterol, lipid and triglyceride contents compared to the animals fed HCD alone. Histological examination of organs of these animals showed severe fatty vacuolation in livers and signet ring type vacuolation in kidneys of rats fed HCD. Taurine showed ameliorating effect on these abnormalities. The animals fed taurine in HCD also showed increased bile and sterol excretion in faeces compared to rats fed HCD alone. Taurine showed significant hypocholesterolemia in rats probably by enhancing the catabolism of cholesterol and reducing the absorption of dietary cholesterol.     

The effect of taurine on cholesterol degradation in mice fed a high-cholesterol diet

The hypocholesterolemic effect of taurine was examined in mice fed a high-cholesterol diet containing 1% cholesterol and 0.25% sodium cholate. Male C57BL/6 mice were divided into 3 groups: control group (HC), 1% taurine-supplemented group (HCT+), and taurine-deficient group (HCT-) produced by supplying 0.5% guanidinoethyl sulfonate (GES) solution ad libitum instead of water. After they were fed with the respective diet or drinking water for 4 weeks, the liver taurine level was reduced 80% in the HCT- group compared with that in the HC group, although there was no difference in the serum taurine amount between the two groups. The formation ratio of cholesterol gallstones increased from 71% to 100% by taurine deficiency, and decreased to 0% by taurine supplementation. Compared with the HC group, serum and liver cholesterol significantly decreased, and the excretion of fecal bile acid notably rose in the HCT+ group but tended to lower in the HCT- group. There were no differences in LDL receptor protein level among the three groups. In the subsequent experiment, triglycerides (TG) secretion rate was determined and found to be significantly suppressed by taurine supplementation. In conclusion, it is suggested that taurine does not up-regulate LDL receptor protein level, and the decrease in cholesterol in the circulation is mainly due to its suppressive effect on TG secretion from the liver.     

Effects of prolonged guanidinoethanesulphonate administration on taurine and other amino acids in rat tissues

In order to deplete tissue taurine, 2-guanidinoethanesulphonate, a structural analogue of taurine was administered in drinking water with taurine-free diet to adult rats for four weeks. As a consequence the taurine concentrations in the blood serum, liver, kidney, spleen, intestine, lung, heart, muscle and cerebellum fell by nearly one half. Threonine, serine, glycine, alanine, methionine, tyrosine, lysine and histidine concentrations increased in blood plasma. Similar changes were also discernible in the heart and muscle. In the kidney and the lung the concentrations of several other amino acids fell as well, though increments occurred in the threonine content in the kidney and in threonine, serine and methionine contents in the lung. Taurine was practically the only amino acid the level of which fell in the liver, spleen, intestine and cerebellum. These findings indicate that 2-guanidinoethanesulphonate combined with taurine-free diet effectively lowers tissue taurine levels, but its action is not specific to taurine. It may be used as a tool to elucidate the physiological functions of taurine in the body.     

Antiatherogenic effect of taurine in high fat diet fed rats

The role of taurine on atherogenesis induced by high fat diet in rats, a species which depends entirely on taurine for conjugation of bile acids has been investigated. Wistar male rats were fed on (p.o.) taurine in addition to high fat diet (11% coconut oil w/w) for 6 months. High fat diet caused significant increase of serum total cholesterol (2 fold), serum triglycerides (92.6%), LDL cholesterol (92.3%) and body weight gain (2.8 fold). Taurine administration significantly reduced serum cholesterol (37%), triglycerides (94.5%), LDL cholesterol (34%), body weight (46%). It also significantly reduced aortic cholesterol and thiobarbituric acid reactive substances and there was a significant increase of reduced glutathione. Taurine significantly increased fecal bile acids which may have resulted in significant decrease of serum cholesterol. Aortic lesion index was significantly decreased in the taurine administered group suggesting the antiatherogenic effect of taurine. It is concluded that taurine attenuated the atherogenesis possibly by its hypocholesterolemic and antioxidant property.     

Effect of selenium deficiency on tissue taurine concentration and urinary taurine excretion in the rat

The purpose of this study was to determine the effect of selenium deficiency on tissue taurine levels and urinary taurine excretion. Weanling male Sprague-Dawley rats were fed selenium-deficient or selenium-adequate diets for 20 weeks. As selenium deficiency developed, urinary taurine excretion increased in selenium-deficient rats compared to controls. At 12 weeks, the selenium-deficient rats excreted 1.7-fold more taurine than control rats. At the same time plasma glutathione peroxidase was 1.2% of control and plasma glutathione was 226% of control. At 20 weeks, renal taurine was decreased but renal glutathione was increased in selenium-deficient rats compared to controls. Feeding the experimental diet for 6 weeks without methionine supplementation caused a fall in urinary taurine excretion. However, there was no difference between selenium-deficient and control rats. These results indicate that selenium deficiency affects renal handling of taurine in the rat when dietary sulfur amino acids are not restricted.     

Actions of guanidinoethane sulfonate on taurine concentration,retinal morphology and seizure threshold in the neonatal rat

Administration of the taurine transport inhibitor, guanidinoethane sulfonate (GES) to pregnant rats depleted taurine concentrations to approximately one-half of normal values in the newborn progeny. By 5 days of age taurine concentrations had returned to normal in all organs tested with the exception of the lungs. Longer postnatal exposure to GES significantly depressed tissue taurine levels. Prenatal exposure to GES had no effect on fetal development or the capability of the newborn rat to biosynthesize or transport taurine. Pre- and postnatal exposure to GES produced a degeneration of the photoreceptor layer of the retina similar to that observed in cats fed a taurine deficient diet. The pentylene tetrazole chemoshock threshold in GES-treated pups was greater than that in control pups. These results indicate that prenatal exposure to GES deplete taurine concentrations in the newborn rat. Morphological changes are thereby produced in the retina of rat that are similar to those observed in animals having limited ability to synthesize taurine which are maintained on a taurine-free diet.     

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.     

Improvement in cholesterol metabolism in mice given chronic treatment of taurine and fed a high-fat diet

The effects of chronic treatment of taurine on hypercholesterolemia and atherosclerosis were examined in C57BL/6J mice fed a high-fat diet containing 15% fat and 1.25% cholesterol. Taurine was dissolved in drinking water at 1% (w/v) and was given to mice ad libitum during 6 months-feeding of a high-fat diet. Hypercholesterolemia occurred and lipid accumulation on the aortic valve was evident. Taurine treatment lowered serum LDL + VLDL cholesterol by 44% in mice fed a high-fat diet, while it elevated serum HDL cholesterol by 25%. As a result, the atherogenic index, the ratio of HDL to LDL + VLDL was markedly improved. Cholesterol content in the liver also decreased by 19% with taurine. Similar tendencies were seen in mice fed regular chow, but the changes were not significant. The area of aortic lipid accumulation, which served as an index of atherosclerosis, was reduced by 20% with taurine. In the liver, taurine doubled the activity of cholesterol 7alpha-hydroxylase. These observations, together with prior findings, suggest that the cholesterol-lowering action of taurine may relate to the increased conversion of cholesterol to bile acids via stimulation of cholesterol 7a-hydroxylase activity. Thus, chronic treatment of high-fat mice with taurine improves the abnormal profile of the serum lipoproteins, and thereby retards the progression of atherosclerosis.     

Comparative regulation of major enzymes in the bile acid biosynthesis pathway by cholesterol, cholate and taurine in mice and rats

These enzymes play important roles in the biosynthesis of bile acids. They are cholesterol 7alpha-hydroxylase (CYP7A1), the rate limiting enzyme in the classic pathway, sterol 12alpha-hydroxylase (CYP8B1), the key enzyme for synthesis of cholic acid (CA), and sterol 27-hydroxylase (CYP27), the initial enzyme in the alternative pathway. In the present study, the susceptibility of these three enzymes to dietary cholesterol and cholate, and the cholesterol lowering effect of taurine were determined in male C57BL/6 mice and Wistar rats. Both mice and rats were divided into 6 groups: control group (N), high cholesterol diet group (C), high cholesterol and cholate diet group (CB), and their 1% taurine-supplemented groups (NT, CT, CBT, respectively). After animals were fed with the respective diets for one week, the mRNA levels of CYP7A1 increased in the C-group compared with those of the N-group, and decreased in the CB-group compared with those of the C-group in both mice and rats. But the extent of decrease is different between the two species. CYP8B1 was also markedly repressed by cholate in mice, but not in rats. These results are consistent with the changes in serum and liver cholesterol concentrations. Taurine significantly increased CYP7A1 mRNA levels in the CBT-group compared with the CB-group in both animal models, with a subsequent decrease in serum and liver cholesterol levels and increase in fecal bile acid excretion. Up-regulated CYP8B1 was also observed after taurine supplementation in the CBT-group in mice. No increase in CYP7A1 was produced by taurine in the CT-group compared with that of the C-group in mice, although the changes of serum and liver cholesterol and fecal bile acids indicated taurine showed an efficient cholesterol lowering effect. In addition, CYP27 was induced in both C- and CB-groups of rats but not of mice, and no changes were produced by taurine. The overall results suggest that there are differences between mice and rats in susceptibility of the three enzymes to dietary cholesterol and cholate, and taurine induced CYP7A1 to produce its cholesterol-lowering effect only in the presence of cholate in the cholesterol diet.     

Dietary taurine enhances cholesterol degradation and reduces serum and liver cholesterol concentrations in rats fed a high-cholesterol diet

Summary.  The effect of taurine on hypercholesterolemia induced by feeding a high-cholesterol (HC) diet (10 g/kg) to rats was examined. When taurine was supplemented to HC for 2 wk, serum total cholesterol significantly decreased and serum HDL-cholesterol increased compared with the HC diet group. In the hypercholesterolemic rats fed the HC diet, the excretion of fecal bile acids and hepatic cholesterol 7α-hydroxylase (CYP7A1) activity and its mRNA level increased significantly, and the supplementation of taurine further enhanced these indexes, indicating an increase in cholesterol degradation. Agarose gel electrophoresis revealed that, in hypercholesterolemic rats fed the HC diet, the serum level of the heavier VLDL increased significantly, but taurine repressed this increase and normalized this pattern. Significant correlations were observed between the time-dependent increase of CYP7A1 gene expression and the decrease of blood cholesterol concentration in rats fed the HC diet supplemented with taurine. These results suggest that the hypocholesterolemic effects of taurine observed in the hypocholesterolemic rats fed the HC diet were mainly due to the enhancement of cholesterol degradation and the excretion of bile acid. Received December 4, 2001 Accepted January 2, 2002 Published online September 10, 2002 Acknowledgment This work was supported by a grant of Taisho Pharmaceutical Co., Ltd (Japan). We thank J. I. Gordon for their generous gifts of cDNAs. Authors' address: Dr. Hidehiko Yokogoshi, School of Food and Nutritional Sciences, The University of Shizuoka, Shizuoka 4228526, Japan, E-mail: yokogosi@u-shizuoka-ken.ac.jp     

Comparison of taurine biosynthesis ability between juveniles of Japanese flounder and common carp

This study was conducted to investigate taurine deficiency and the ability of taurine biosynthesis in both juvenile Japanese flounder (JF) and juvenile common carp (CC) in vivo using low taurine level diets. Three different taurine level diets were prepared by the supplementation of taurine to the basal composition (JF--0, 0.5 and 1.5% in JF; CC--0, 1, 3% in CC). The final average body weight and feed efficiency of JF fed the JF - 1.5% was significantly higher than those of fish fed on the JF--0%. On the other hand, no significant difference was observed in CC fed with CC--0, 1, and 3% diets. The taurine retention rate was negative in the case of JF-fed with the taurine-free supplement (JF--0%). On the other hand, the taurine retention rate was about 280% in the case of CC-fed with the taurine-free supplement (CC--0%). These findings indicate that while taurine is essential for growth of JF, it is not essential for the growth of CC.     

Dietary taurine potentiates polychlorinated biphenyl-induced hypercholesterolemia in rats*

The effect of dietary taurine on cholesterol metabolism and the distribution of lipoprotein-cholesterol in serum of rats fed a diet containing polychlorinated biphenyls (PCB) was examined. Young male Wistar rats (60 g) were fed diets containing 0.2 g/kg diet of PCB and/or 30 g/kg diet of taurine for 15 days. The experiment was performed as the 2 (PCB) x 2 (taurine) factorial design. The addition of PCB elevated serum levels of total- and HDL-cholesterol and apolipoprotein A-I, which is a major apolipoprotein of HDL. Simultaneous supplementation of taurine with PCB amplified the increase of the serum level of total- and HDL-cholesterol. Hepatic concentrations of cholesterol and total lipids were significantly elevated by the supplementation of PCB, and taurine significantly amplified these increases caused by PCB. PCB suppressed hepatic cholesterol 7alpha-hydroxylase (CYP7A1) gene expression, and taurine induced CYP7A1 gene expression. Taurine also enhanced PCB-induced elevation of malic enzyme mRNA in the liver. These results suggest that taurine enhanced PCB-induced hyper-alpha-cholesterolemia and that taurine has a role in increasing HDL-cholesterol.     

Improving effect of dietary taurine on marked hypercholesterolemia induced by a high-cholesterol diet in streptozotocin-induced diabetic rats

The effect of dietary taurine on hypercholesterolemia induced by a high-cholesterol diet in streptozotocin (STZ)-induced diabetic rats was investigated. The concentrations of serum and liver cholesterol were markedly elevated in STZ-diabetic rats fed on the cholesterol-containing diet, and dietary taurine significantly reduced this elevated level of cholesterol in the serum and liver. The gene expression of cholesterol 7 alpha-hydroxylase (CYP7A1), which is the rate-limiting enzyme for cholesterol degradation, was induced by the supplementation of taurine to the high-cholesterol diet. It is suggested that one of the reasons for this hypocholesterolemic action by taurine might have been the enhancement of cholesterol degradation.     

Effect of dietary sulfur amino acids on the taurine content of rat tissues

Summary.  The effect of dietary sulfur amino acids on the taurine content of rat blood and tissues was investigated. Three types of diet were prepared for this study: a low-taurine diet (LTD), normal taurine diet (NTD; LTD + 0.5% Met), and high-taurine diet (HTD; LTD + 0.5% Met + 3% taurine). These diets had no differing effect on the growth of the rats. The concentration of taurine in the blood from the HTD- and NTD-fed rats was respectively 1,200% and 200% more than that from LTD-. In such rat tissues as the liver, the taurine content was significantly affected by dietary sulfur amino acids, resulting in a higher content with HTD and lower content with LTD. However, little or no effect on taurine content was apparent in the heart or eye. The activity for taurine uptake by the small intestine was not affected by dietary sulfur amino acids. The expression level of taurine transporter mRNA was altered only in the kidney under these dietary conditions: a higher expression level with LTD and lower expression level with HTD. Received January 8, 2002 Accepted January 18, 2002 Published online August 20, 2002 Authors' address: Dr. Hideo Satsu, Laboratory of Food Chemistry, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan, Fax: +81-3-5841-8026 E-mail: asatsu@mail.ecc.u-tokyo.ac.jp Abbreviations: HTD, high-taurine diet; NTD, normal taurine diet; LTD, low-taurine diet; TAUT, taurine transporter; CSA, cysteine sulfinate; CDO, cysteine dioxygenase; CSAD, cysteine sulfinate decarboxylase; PBS, phosphate-buffered saline; DIDS, 4,4′-diisothiocyanostilbene-2′,2′-disulfonic acid     

The effect of taurine depletion with guanidinoethanesulfonate on bile acid metabolism in the rat

Administration of guanidinoethanesulfonate (GES) to male rats for 5 weeks resulted in a 90% decrease in the hepatic taurine concentration. This depletion of hepatic taurine was associated with a 570% increase in the concentration of glycine-conjugated bile acids, a 30% decrease in the concentration of taurine-conjugated bile acids, and an increase in the ratio of glycine- to taurine-conjugated bile acids from 0.046 to 0.45. The total concentration of bile salts in the bile and the turnover of cholic acid were not affected by administration of GES. The data indicate that the taurine-depleted rat conserves taurine to some extent by using glycine instead of taurine for bile salt synthesis but not by decreasing the daily fractional turnover of bile acids.     

Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease

The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD.     

Role of feline maternal taurine nutrition in fetal cerebellar development: An immunohistochemical study

Summary We report the effects of four levels of maternal dietary taurine on the cerebellum of 45-day gestation fetuses. As we have previously reported for newborn and 8-week-old kittens, maternal dietary taurine content has a profound effect also on fetal cerebellum. Fetuses from queens fed the lowest amount of taurine had the greatest density of granule cells, probably because of smallest brain size, and had a high proportion of morphological abnormalities. Somewhat surprising was the observation that the fetuses from the lowest maternal dietary taurine group had the highest proportion of taurine-positive granule cells. In addition, these results confirm the vulnerability of developing fetal brain to its intrauterine environment.