Effect of dietary taurine on endogenous hypercholesterolemia in rats fed on phenobarbital-containing diets.

The effect of dietary taurine on endogenous hypercholesterolemia induced by a phenobarbital-containing diet was investigated. Supplemented taurine did not affect the concentrations of serum cholesterol, but further potentiated the accumulation of hepatic cholesterol in the hypercholesterolemic state induced by phenobarbital. It is suggested that taurine might amplify the hepatic cholesterogenesis in phenobarbital-induced hypercholesterolemia.     

The effect of taurine on cholesterol metabolism

The elevated plasma cholesterol level, in particular, LDL cholesterol is regarded as an important risk factor for the development of atherosclerosis and coronary artery disease. A number of studies provide the evidence that taurine has the efficient action to reduce plasma and liver cholesterol concentrations, especially to decrease VLDL and LDL cholesterol in hypercholesterolemia animal induced by high cholesterol diet. Cholesterol lowering effect of taurine is actually involved in the regulatory mechanism of cholesterol and bile acid homeostasis that mediated by CYP7A1, which has become a biomarker for cholesterol metabolism and itself is also regulated by several factors and nuclear receptors. This review summarizes the change of cholesterol concentration in metabolism observed in feeding studies of hypercholesterolemia animal dealing with taurine, and then, addresses the possible metabolic and molecular mechanisms of cholesterol lowering effect by taurine in three aspects, cholesterol clearance from blood circulation, bioconversion of cholesterol to bile acid in liver, and excretion of cholesterol and bile acid from intestine.     

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 7α-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.     

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.     

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.     

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     

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.     

Role of plasma and liver cholesterol- and lipoprotein-metabolism determinants in LpX formation in the mouse

Cholestasis is characterized by hypercholesterolemia and the appearance of an abnormal lipoprotein, lipoprotein X (LpX), in plasma. The mechanisms responsible for this cholestatic plasma lipid phenotype are not fully understood. We used ATP-binding cassette A1 (ABCA1)-/- and scavenger receptor class B type I (SR-BI)-/- mice to test the hypothesis that hepatic sinusoidal cholesterol transporters contribute to LpX formation and hypercholesterolemia during cholestasis. Bile-duct ligation (BDL) of both ABCA1-/- and SR-BI-/- mice, as well as their respective controls, induced a dramatic increase in plasma cholesterol and phospholipid concentrations. Plasma fractionation revealed the presence of LpX in plasma of cholestatic mice, irrespective of their genetic background. We observed that the presence of HDL before cholestasis, a decrease in the activity of LCAT, and an increase in VLDL synthesis were not required for hypercholesterolemia and lipoprotein modifications induced by obstructive cholestasis in mice. In addition, murine cholestasis resulted in increased hepatic cholesterol synthesis that may contribute to the higher plasma free cholesterol levels found during the early hours after BDL. Together these findings indicate that hypercholesterolemia and LpX formation associated with obstructive cholestasis are correlated with an increase in hepatic cholesterol synthesis and are independent of plasma HDL levels, LCAT activity, VLDL synthesis, and ABCA1 and SR-BI expression.     

Effects of Sulfur-containing Amino Acids and Glycine on Plasma Cholesterol Level in Rats Fed on a High Cholesterol Diet

The effects of the addition of individual amino acids on methionine-induced hypercholesterolemia (experiment 1), and the interacting effects of dietary protein level and sulfur-containing amino acids and glycine on plasma cholesterol concentration (experiment 2) were studied in growing rats fed on a high cholesterol diet. In experiment 1, rats were fed on a 25% casein-0.75% methionine (25CM) diet containing 2.5% of individual amino acids for 2 weeks. Methionine-induced hypercholesterolemia was prevented by the concurrent addition of glycine or serine, but the other amino acids tested (alanine, threonine, leucine, phenylalanine, lysine, arginine, and glutamic acid) had no effect. Histidine rather enhanced the hypercholesterolemia. In experiment 2, rats were fed on a 10%, 25%, or 50% casein diet containing 0.75% methionine, 0.60% cystine, 0.63% taurine, 2.5% glycine, or 0.75% methionine +2.5% glycine for 3 weeks. Dietary addition of 0.75% methionine increased the plasma cholesterol concentration for the 25% and 50% casein diets, but it decreased the plasma cholesterol for the 10% casein diet. When the addition level of methionine was doubled in the 10% casein diet, the plasma cholesterol concentration was significantly higher for the 1.5% methionine-added diet than for the 0.75% methionine-added diet. Cystine and taurine lowered plasma cholesterol for all dietary casein levels. Methionine-induced hypercholesterolemia with 25% and 50% casein diets was prevented by the glycine supplementation. These data suggest that sulfur-containing amino acids and glycine are important in plasma cholesterol regulation.     

Effect of red wine on oxidative stress and hypercholesterolemia induced by feeding a high-cholesterol diet in rat

The effect of red wine on oxidative stress and hypercholesterolemia induced by feeding a high-cholesterol diet (supplemented with 1.65% of cholesterol (w/w) for 4 weeks) to female Wistar rats was examined. When red wine was simultaneously supplemented to high-cholesterol diet, total cholesterol, triglycerides, atherogenic index and lipid peroxidation products significantly decreased compared with the high-cholesterol diet alone, while GSH content and antioxidative enzymes activities were enhanced. In the hypercholesterolemic rat the excretion of fecal bile acids, as well as their plasma and hepatic concentrations were increased significantly. Administration of red wine enhanced these values, indicating an increase in the cholesterol degradation. These results suggest that red wine may have a protective effect against oxidative stress, hypercholesterolemia and atherogenic index induced by high-cholesterol diet.     

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.     

Prevention of hypercholesterolemia and atherosclerosis in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail by taurine supplementation

The effects of taurine supplementation on the serum cholesterol levels and the progression of atherosclerosis were investigated in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail. The ingestion of a high-cholesterol diet containing 1% cholesterol by LAP quails for 60 days resulted in a marked elevation in serum non-HDL cholesterol and triglyceride, as well as severe aortic lesions with lipid droplets. An immunohistochemical study showed that the lesion consisted of mainly lipid-rich macrophages and T cells. Sixty-day taurine supplementation (1% in drinking tap water) to LAP quails fed high-cholesterol diet containing 1% cholesterol significantly reduced serum non-HDL cholesterol from 4,549 to 2,350 mg/dl. The serum triglyceride level also decreased after taurine supplementation from 703 to 392 mg/dl. Although the HDL cholesterol level significantly decreased due to the high-cholesterol diet, it recovered to the control level fed a regular diet in response to taurine. Bile acid production was stimulated and hepatic cholesterol was reduced by taurine supplementation. A quantitative analysis using aortic cross-sections showed that areas of oil-red O positive lipid accumulation significantly decreased by 74% after taurine supplementation. These results demonstrated the lipid-lowering and anti-atherosclerotic effects of taurine in a diet-induced hyperlipidemic LAP quail model. The prevention of atherosclerosis by taurine is mainly attributed to an improvement in the serum cholesterol and triglyceride levels, which may be related to changes in the hepatic cholesterol metabolism.     

Hypocholesterolemic effect of rice protein is due to regulating hepatic cholesterol metabolism in adult rats

Aging is one of major risk factors for developing hypercholesterolemia. To elucidate the cholesterol-lowering mechanism exerted by rice protein (RP), the effects on hepatic cholesterol outputs and cholesterol metabolism related enzymes were investigated in adult rats, which were fed by casein (CAS) and RP without cholesterol in diets. After 2 weeks of feeding, the significant cholesterol-lowering effect was observed in adult rats fed by RP compared to CAS. The hepatic total- and VLDL-cholesterol secretions into circulation were significantly depressed in RP group, whereas biliary outputs of bile acids and cholesterol were effectively stimulated by RP-feeding, causing an increase in fecal sterol excretion compared to CAS. As a result, the apparent cholesterol absorption was significantly inhibited by RP. RP-feeding significantly increased the activity and gene expression of cholesterol 7α-hydroxylase, whereas acyl-CoA:cholesterol acyltransferase-2 activity and gene expression were significantly decreased by RP as compared with CAS. Neither activity nor gene expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase of RP did differ from CAS in the liver. The present study demonstrates that rice protein can prevent hypercholesterolemia through modifying hepatic cholesterol metabolism under cholesterol-free dietary condition. The findings suggest that hypocholesterolemic action induced by rice protein is attributed in part to the inhibition of cholesterol absorption during the adult period.     

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.     

Effects of gender on hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and LDL receptor in hereditary analbuminemia

Hypoalbuminemia is accompanied by hypercholesterolemia in both nephrotic syndrome and hereditary analbuminemia. Hypercholesterolemia is more severe in the female than in the male Nagase analbuminemic rats (NAR). The sex difference in plasma cholesterol diminishes after ovariectomy (OVX) and reappears after estrogen replacement in the NAR. The molecular mechanism responsible for the sex difference in severity of hypercholesterolemia in NAR is not known and was investigated here. To this end, hepatic hydroxylmethylglutaryl (HMG)-CoA reductase, cholesterol 7alpha-hydroxylase, and LDL receptor were determined in male, female, and OVX female NAR and Sprague-Dawley (SD) rats. Plasma cholesterol, triglycerides, and hepatic HMG-CoA reductase activities were greater in both female and male NAR than in SD rats. This was coupled with upregulation of cholesterol 7alpha-hydroxylase in both male and female NAR compared with SD controls. LDL receptor in male NAR was similar to that in male SD rats but was significantly reduced in female NAR. OVX partially, but significantly, reduced plasma cholesterol and triglyceride levels in female NAR. This was coupled with a significant rise in hepatic cholesterol 7alpha-hydroxylase and a modest increase in hepatic LDL receptor. In contrast, OVX resulted in a mild elevation of plasma cholesterol and no significant changes in total hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, or LDL receptor in female SD rats. Thus the greater severity of hypercholesterolemia in the female NAR appears to be due, in part, to a combination of the constrained compensatory upregulation of cholesterol 7alpha-hydroxylase and LDL receptor deficiency.     

Diosgenin regulates cholesterol metabolism in hypercholesterolemic rats by inhibiting NPC1L1 and enhancing ABCG5 and ABCG8

Hypercholesterolemia is a preventable risk factor for atherosclerosis and cardiovascular disease. However, the mechanisms of diosgenin (DG) that promote cholesterol homeostasis and alleviate hypercholesterolemia remain elusive. To investigate the effects and molecular mechanisms of the promotion of cholesterol metabolism by DG, a rat model of hypercholesterolemia was induced by providing a high-fat diet for 4 weeks. After 4 weeks, the rats were intragastrically administered high-dose DG (0.3 g/kg/d), low-dose DG (0.15 g/kg/d) or simvastatin (4 mg/kg/d) once a day for 8 weeks. The serum and hepatic cholesterol were tested, the mRNA and protein expression levels of Niemann-Pick C1-Like 1 (NPC1L1), liver X receptor-α (LXR-α) and the ATP-binding cassette G5/G8 (ABCG5/G8) transporters were measured. The results indicate that DG could reduce body weight, decrease the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, liver total cholesterol and free cholesterol levels compared to those in the controls. Simultaneously, liver tissue pathological morphology analyses revealed that DG could attenuate hepatic steatosis compared to that in the high-fat diet group. Further investigation demonstrated that DG significantly decreased the expression of NPC1L1 and LXR-α in the intestine and markedly increased the expression of ABCG5/G8 in the liver and intestine. Compared to the high-fat diet group, the rats in the DG-treated groups ameliorated hypercholesterolemia in a dose- and time-dependent manner. These data suggest that DG may not only inhibit intestinal cholesterol absorption by downregulating NPC1L1 but also enhance cholesterol excretion by increasing the expression of ABCG5/G8. DG could be a new candidate for the prevention of hypercholesterolemia.     

Effect of heparin and adrenocorticotropin on the hepatic and serum cholesterol in catfish, Heteropneustes fossils.

The administration of heparin with or without ACTH significantly decreased hepatic cholesterol content in catfish. In serum, heparin alone produced first hypercholesterolemia which was followed by hypocholesterolemia whereas it potentiated hypercholesterolemic action of ACTH three hours after administration. It is concluded that heparin normally caused hypercholesterolemia by releasing cholesterol from liver as lipoprotein complex. The hypocholesterolemic action of heparin might be an indirect one.     

Age-related changes in cholesterol metabolism in macrosomic offspring of rats with streptozotocin-induced diabetes.

The aim of this study was to determine the impact of diabetic macrosomia on cholesterol and lipoprotein metabolism. Age-related changes in the activities of serum LCAT, hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and ACAT, the major enzymes involved in cholesterol metabolism, were determined in macrosomic offspring of streptozotocin-induced diabetic rats. Hepatic, serum, and lipoprotein cholesterol contents were also examined. Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, macrosomic pups had higher serum, LDL-HDL(1), and HDL(2-3) cholesterol levels (P < 0.05) associated with increased LCAT activity (+57%) compared with control values. At 1 and 2 months of life, serum and lipoprotein cholesterol concentrations in macrosomic rats were similar to those of controls, whereas LCAT activity remained elevated about 1.5-fold. In addition, there was no change in hepatic cholesterol contents but hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and ACAT activities were higher in both macrosomic males and females than in their respective controls (P < 0.01). By 3 months, macrosomic rats had developed hypercholesterolemia with a rise in all lipoproteins. Enzyme activities were still increased in these mature macrosomic rats, and hepatic cholesteryl esters were higher only in macrosomic females.These data demonstrate an overproduction, combined with overutilization, of cholesterol during the phase of rapid growth in macrosomic rats. However, cholesterol oversynthesis exceeded its removal and was a major contributor to hypercholesterolemia in adult macrosomic rats. In conclusion, macrosomia was associated with alterations in cholesterol metabolism through adulthood.     

牛磺酸抗小鼠动脉粥样硬化的研究

为了探讨牛磺酸抗小鼠动脉粥样硬化的影响及可能机制,将C57BL/6J小鼠分成五组,正常对照组给予基础饲料喂养,高脂组给予高脂饲料,牛磺酸组分别给予含1.0%、3.0%和5.0%牛磺酸的高脂饲料,实验时间为90d。结果表明,高脂组小鼠主动脉内膜和肝脏发生了粥样硬化病变和脂肪变性,而牛磺酸组病变程度随剂量增大而减轻。高脂组较正常对照组血清及肝脏甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-c)、动脉硬化指数(AI)显著升高,高密度脂蛋白胆固醇(HDL-c)显著降低;牛磺酸组较高脂组显著改善。可见牛磺酸可通过改善脂质代谢紊乱发挥抗动脉粥样硬化的作用。     

Dissociation between cholesterol secretion and plasma lipid transfer activity in rabbits

Human and rabbit plasma contains a lipid transfer protein that transfers cholesteryl esters and triglycerides among the plasma lipoproteins and may also have a role in the movement of lipids into and out of cells. Little is known about the regulation of the activity of the lipid transfer protein, but in the rabbit, hypercholesterolemia is associated with increased plasma lipid transfer activity (LTA). Perfused rabbit livers secrete LTA, and hepatic cholesterol secretion is increased in rabbits with diet-induced hypercholesterolemia. Thus, experiments were performed with rabbits to determine if LTA is regulated by a concerted hepatic secretion of lipoprotein protein cholesterol and LTA. Rabbits were fed chow or chow plus coconut oil (14% wt/wt), and plasma lipids, LTA, and the rate of secretion of cholesterol into plasma were determined. Coconut oil feeding increased plasma cholesterol by 68%, LTA by 42%, and hepatic cholesterol secretion by 69%. Mevinolin (75 mg/day), an inhibitor of cholesterol biosynthesis, lowered LTA and plasma cholesterol without affecting the rate of secretion of cholesterol into plasma. These studies provide further evidence that, in the rabbit, plasma cholesterol and LTA are closely related, and the association is not likely to be caused by a concerted hepatic secretion of cholesterol and LTA.