Effect of blackgram fibre on ethanol-induced hyperlipidemia in rats

Rats fed a diet low in fibre and provided with ethanol for 4 weeks showed a higher concentration of cholesterol in the serum, liver and heart, but not in the aorta when compared with control rats not provided with ethanol. Animals maintained on a diet of blackgram fibre (30%) and provided with ethanol had significantly lower concentration of cholesterol in these tissues and in the aorta. The concentration of triglyceride was also raised in the serum, liver and heart in rats fed a diet low in fibre + ethanol. A diet of blackgram fibre caused a significant decrease in serum and liver triglyceride. Fecal excretion of neutral sterols and bile acids decreased in rats fed a diet low in fibre + ethanol, whereas blackgram fibre caused an increase in such fecal excretion.     

肝脏表达Niemann-Pick C1-Like 1调节肝X受体诱导的小鼠胆固醇分泌

目的:探讨小鼠肝脏过表达人NPC1L1对LXR诱导的小鼠胆固醇分泌的影响。方法:给予野生型小鼠(WT)和肝脏过表达人NPC1L1的转基因小鼠(L1Tg)胃饲LXR激动剂(T0901317)7 d后,抽提小鼠粪便总脂质并检测核心甾醇的含量,检测小鼠的血浆脂质水平,分析肝脏ABCG5和ABCG8的mRNA表达水平。结果:L1Tg小鼠与WT小鼠相比,除血浆游离胆固醇含量显著升高外,粪便核心甾醇含量及肝脏ABCG5和G8的mRNA水平差异无统计学意义;在胃饲T0901317 1 w后,WT小鼠的粪便核心甾醇含量由[(3.22±0.44)升高到(28.68±1.05)μmol.d-1.100 g-1],血浆总胆固醇、游离胆固醇、胆固醇酯和磷脂的含量均显著升高,同时肝脏的ABCG5和G8的mRNA水平也分别上调了5倍和2倍;然而,L1Tg小鼠经T0901317处理后,与T0901317处理的WT小鼠相比,粪便核心甾醇的分泌减少了56%,血浆游离胆固醇含量升高了40%,肝脏的ABCG5和G8的mRNA水平分别降低了52.4%和40.6%。结论:肝脏特异表达人NPC1L1降低了LXR诱导的小鼠粪便核心甾醇的分泌,并升高了血浆游离胆固醇水平,可能与下调LXR诱导的肝脏ABCG5和G8 mRNA表述水平有一定关系。     

Dietary fiber and cholesterol metabolism in rats fed a high cholesterol diet.

The effect of administering blackgram (Phaseolus mungo) fiber (isolated as neutral detergent residue) at the 30% dietary level has been studied with regard to lipid concentration in the tissues and that of biliary and fecal bile acids and sterols. Rats were fed a high fat-cholesterol diet and compared with those fed a cellulose diet. The results indicate that blackgram fiber significantly lowers cholesterol in both serum and aorta [11]. There was an increased concentration of biliary sterols and bile acids and increased fecal excretion of sterols and bile acids, each of these effects being significantly greater than those observed in the rats fed cellulose.     

Fecal neutral sterols in omnivorous and vegetarian women

The purpose of this study was to investigate the effect of a vegetarian diet on human fecal neutral sterol excretion. Free and esterified fecal neutral sterols were analyzed by capillary gas-chromatography in healthy North-American white women who were consuming either a mixed Western diet (n = 19) or a vegetarian diet (n = 20). Vegetarians had lower mean concentrations of bacterial metabolites of cholesterol, coprostanol, and coprostanone, and their relative amounts of esterified neutral sterol metabolism in both populations. Most of the subjects in both groups excreted their neutral sterols mainly as metabolites. However, 25% of the omnivores and 21% of the vegetarians had exceptionally low amounts of these metabolites in their feces. The vegetarians in this study differed only slightly from omnivores with regard to intestinal bacterial metabolism of neutral sterols.     

Casein-induced hypercholesterolaemia in rabbits is calcium-dependent

Young male rabbits were fed semi-purified diets containing either casein or soy protein, both at a normal (0.84%, w/w) and a high (1.44%, w/w) level of dietary calcium. At the normal calcium level, casein, as compared with soy protein, increased the concentration in serum of total and free cholesterol and the ratio of free cholesterol to phospholipid. Also, casein increased the intestinal phosphate absorption and decreased the faecal fat excretion. The hypercholesterolaemic response of the rabbits on the casein diet was significantly correlated with both phosphate absorption (r = +0.744) and fat excretion (r = -0.701). The increased amount of dietary calcium inhibited the casein-specific effects on both the intestinal and the serum lipid parameters. In contrast, calcium did not change these parameters in rabbits fed the soy protein diet. These results support the hypothesis that the degree of phosphorylation of casein is involved in the mechanism of the casein-induced hypercholesterolaemia by means of its effect on the enterohepatic cycle of bile acids.     

Influence of casein versus soy protein isolate on lipid metabolism of minipigs

This report describes whether a complete exchange of soy protein isolate for casein affects serum lipid or lipoprotein levels. For this purpose, 10 adult minipigs underwent two 6-week crossover experiments, one with 11 and one with 22 weight % protein in a western-style diet. Cholesterol levels were 2.02 +/- 0.06 and 1.98 +/- 0.04 mmol/l with casein and soy, respectively (22 weight %) and 2.08 +/- 0.06 and 2.04 +/- 0.05 mmol/l, respectively (11 weight %). There was a significant rise of high-density lipoprotein cholesterol by the lower protein intake, both with casein and soy. In all experiments nitrogen balance was positive. Soy feeding was accompanied by a significant rise of fecal bacterial protein excretion, as calculated from diaminopimelic acid. In summary, no statistically significant difference of plasma or low-density lipoprotein cholesterol levels were observed, neither due to the kind nor to the amount of dietary protein.     

Fecal Neutral Sterols in Omnivorous and Vegetarian Women

The purpose of this study was to investigate the effect of a vegetarian diet on human fecal neutral sterol excretion. Free and esterified fecal neutral sterols were analyzed by capillary gas-chromatography in healthy North-American white women who were consuming either a mixed Western diet (n = 19) or a vegetarian diet (n = 20). Vegetarians had lower mean concentrations of bacterial metabolites of cholesterol, coprostanol, and coprostanone, and their relative amounts of esterified neutral sterols were higher. There was a considerable variation in the extent of neutral sterol metabolism in both populations. Most of the subjects in both groups excreted their neutral sterols mainly as metabolites. However, 25% of the omnivores and 21% of the vegetarians had exceptionally low amounts of these metabolites in their feces. The vegetarians in this study differed only slightly from omnivores with regard to intestinal bacterial metabolism of neutral sterols.     

Prevention of hypercholesterolemia and atherosclerosis in Japanese quail by high intake of soy protein

This study was undertaken to determine the influence of levels of soy protein on cholesterol metabolism and the development of atherosclerosis in Japanese quail (Coturnix coturnix japonica). Quail were fed purified diets containing one of four levels (10, 20, 40 or 60%) of soy protein either with (atherogenic) or without (control) 0.5% cholesterol. Results showed that higher proportions of protein (40 and 60%) in atherogenic diets had a preventive effect on the development of atherosclerosis in adult male quail. For the atherogenic diets the higher protein levels resulted in significantly lower serum and aorta cholesterol concentrations than observed with the 10 or 20% protein levels and free of aortic atherosclerosis. A dual isotope technique was used to measure the absorption rates for cholesterol in quail fed with 20 and 40% soy protein. Absorption rates were not affected by the level of dietary protein but were influenced by the presence of dietary cholesterol. Relative rates were 40% in quail fed control diets and 30% in quail fed atherogenic diets. The excretion of neutral sterols, largely cholesterol, and bile acids increased with the high intake of soy protein. These results demonstrate that in quail the presence of higher dietary levels of soy protein has both a hypocholesterolemic action and a preventive effect on cholesterol-induced atherosclerosis and one of the possible mechanisms is through increased excretion of cholesterol.     

Cholesterol absorption and sterol balance in normal subjects receiving dietary fiber or ursodeoxycholic acid

Twelve normal subjects were placed on a constant diet and evaluated during three treatment periods, each lasting four weeks. Patients received regular diet alone during period A, regular diet plus 60 g/day wheat bran during period B, and regular diet plus 15 mg/kg/day ursodeoxycholic acid during period C. Cholesterol absorption, plasma lipid concentration, daily fecal excretion of neutral and acidic sterols, and sterol balance were determined following each treatment. No changes in serum lipid levels are observed in the three study periods. Bran administration increases fecal neutral sterol excretion and decreases cholesterol absorption (from 50.1 to 42.0%) with respect to period C. Ursodeoxycholic acid administration has no effect on fecal neutral sterol excretion, whereas bile acid excretion is markedly increased. Sterol balance (evaluated as neutral and acidic fecal sterols excreted per day minus dietary cholesterol plus ursodeoxycholic acid given per day) is lower during ursodeoxycholic acid feeding (360±145 mg/day) than during bran feeding (593±174 mg/day). In conclusion, ursodeoxycholic acid decreases sterol balance values; bran-rich diet increases sterol balance and reduces cholesterol absorption.     

Effects of feeding cholesterol and mixed plant sterols on the fecal excretion of acidic steroids in rhesus monkeys

The effects of feeding diets with high or low amounts of cholesterol and with low or high levels of mixed plant sterols (sitosterol: campesterol: stigmasterol, 60:35:5) on the daily fecal excretion of acidic steroids were studied in rhesus monkeys. During periods of low dietary plant sterol, total fecal acidic steroid excretion was 43% lower (P less than 0.01) during low dietary cholesterol than during high dietary cholesterol. During periods of high dietary plant sterols the fecal acidic steroid excretion was 113% higher (P less than 0.01) with low dietary cholesterol than with high dietary cholesterol. Addition of mixed plant sterols to the low-cholesterol diet produced nearly a 2-fold increase (P less than 0.005) whereas, such an addition to the high cholesterol diet produced a significant decrease by about 53% (P less than 0.025) in the total fecal acidic steroid excretion. The results suggest that the effect of cholesterol feeding on fecal acidic steroid excretion depends on the level of plant sterols in the diet. This interaction of the effects of cholesterol and plant sterols on the fecal acidic steroid excretion is probably related to the inhibitory effect of plant sterols on cholesterol absorption.     

Serum lipids, lipoprotein composition and liver cholesterol in genetically obese Zucker rats fed semipurified diets containing either casein or soy protein

The effect of semipurified diets containing either casein or soy protein on serum lipids, lipoprotein composition and liver cholesterol was studied in genetically obese Zucker rats. The ingestion of a cholesterol-enriched semipurified diet containing casein resulted in elevated levels of serum cholesterol and phospholipids compared to the feeding of a soy protein diet. No differences in serum triglycerides were observed. Differences in serum cholesterol and phospholipids were mainly reflected in the very low density lipoproteins and low density lipoproteins and to a minor extent in the high density lipoproteins. Liver cholesterol paralleled the levels of cholesterol in the serum, the rats fed casein exhibited markedly higher levels of liver cholesterol than those fed soy protein. Furthermore, the rats fed casein also had enlarged livers. Thus, this study clearly shows the differential cholesterolemic effect of dietary casein and soy protein in genetically obese Zucker rats.     

Effect of soy fiber and soy protein on cholesterol metabolism and atherosclerosis in rabbits

The effect of dietary fiber isolated from dehulled, defatted soybean seeds on cholesterol (CHOL) metabolism and atherosclerosis in rabbits was studied alone and in combination with isolated soy protein (ISP). Soy fiber (SF) contains both cellulosic and non-cellulosic dietary fiber. Based on the official AOAC method, soy fibers contains 75% total dietary fiber. Rabbits at 6 months of age were randomly assigned to 1 of 4 dietary treatments. All rabbits received either a casein or ISP-based diet with cellulose or SF as the only dietary fiber source for 36 weeks. Fasting blood samples and feces were collected and analyzed for lipids from individual rabbits. The entire aorta was removed and fixed, and sudanophilic stained lesions were examined visually. Rabbits consuming the SF and/or ISP diets had lower plasma CHOL levels and lower incidence of atherosclerotic lesions relative to the rabbits fed the casein-based cellulose diets. Rabbits consuming the SF and/or ISP diets also had a lower CHOL content in their liver and heart. Rabbits fed ISP-based diets had consistently increased fecal bile acid excretion, whereas rabbits fed diets containing SF had increased fecal and cholesterol concentration. These results suggest a complementary role for SF and ISP in preventing atherosclerosis in rabbits.     

Short- and long-term effects of hypocaloric diets containing proteins of different sources on plasma lipids and apoproteins of obese subjects

The influence of caloric restriction on lipid profile is controversial. This study was designed to evaluate the influence of dietary proteins from different sources on lipoprotein levels in obese subjects during a period of very low-caloric diet followed by 60 days of hypocaloric diet. The subjects were 24 obese patients aged 25-42 of at least 50% above ideal weight. The patients were separated into two groups and received for 15 days 375 kcal/day on the assumption that commercial textured preparations contained the same amount of proteins, respectively, as casein (group A) or soy protein (group B). Then the very low-caloric diet of the two groups was integrated with 425 kcal/day for 60 days. Body weight reduction was equivalent in the two groups. Total plasma cholesterol decreased significantly in both groups after the two periods of diet, but the percent variations were always significantly higher in the group B than in A. Total plasma triglycerides reduced significantly only in the group B. Very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol behaved as total cholesterol in the two groups. High-density lipoprotein (HDL) cholesterol diminished significantly only after the 15 days of very low-caloric diet in group B, while it decreased throughout the diet in group A. The decrease of HDL cholesterol was mainly due to the HDL2 subfraction. The results of our study show that the substitution of soy protein for casein can be of benefit in those patients who need a long-term hypocaloric diet.     

The hypocholesterolemic action of the undigested fraction of soybean protein in rats

Soybean protein was exhaustively digested with endo- and exo-type microbial proteases and the effect of the digestible low molecular fraction (LMF) and the undigested high molecular fraction (HMF) on the serum cholesterol level was compared to that of the intact protein in rats given a cholesterol-enriched diet. The HMF, peptides relatively abundant in hydrophobic amino acids, was found to be substantially hypocholesterolemic when fed at the nitrogen level equivalent to that of the 20% soybean protein diet, and not only serum but also liver cholesterol levels were similar to those usually encountered in rats given diets free of cholesterol. There was a dose-dependent reduction of serum and liver cholesterol when casein was replaced stepwise with HMF. The cholesterol-lowering action could be attributable to an increased fecal steroid excretion.     

Influence of fish protein as compared to casein and soy protein on serum and liver lipids, and serum lipoprotein cholesterol levels in the rabbit

Serum and hepatic cholesterol and triglyceride levels, and serum lipoprotein cholesterol were investigated in rabbits fed fish protein as compared to casein and soy protein as part of a 20% protein, low fat, cholesterol-free, semi-purified diet. A nonpurified diet was used as a control. After a 28-day experimental period, rabbits fed casein developed hypercholesterolemia compared to those fed the soy protein diet. Serum cholesterol levels of rabbits fed fish protein was intermediate and not different from that of the casein or the soy protein group. However, serum triglycerides were higher in the fish group than in the casein group. Feeding of fish protein resulted in a reduction of hepatic cholesterol compared to casein, indicating no direct relationship between serum and hepatic cholesterol. In addition, fish protein induced a decrease of cholesterol in the low density lipoproteins (LDL) compared to casein and an increase of cholesterol in the high density lipoproteins (HDL) compared to casein and soy protein. Reduction in LDL-cholesterol (LDL-C) and elevation in HDL-cholesterol (HDL-C) caused a 10-fold decrease in the LDL-C/HDL-C ratio of fish protein fed rabbits compared to those fed casein. This ratio was similar to that observed with soy protein which was also lower than the ratio of the casein group. Thus, since the LDL-C/HDL-C ratio has been shown to be a good indicator of the atherosclerosis risk, these results suggest that fish protein, as well as soy protein, may reduce the risk of atherosclerosis in rabbits, compared to casein.     

Gelatin intake increases the atheroma formation in apoE knock out mice

The effect of gelatin ingestion on cholesterol metabolism and on atheroma formation was evaluated in both wild type (n=14) and apoprotein E (apoE) knock out (apoE(-/-)) (n=20) C57BL/6 7-week-old mice. Animals were fed a cholesterol-free isoproteic semi-purified diet containing 20% of casein (control diet) or 10% of casein plus 10% of gelatin (gel diet) for 8 weeks. In wild type mice, dietary gelatin caused a reduction in the serum triacylglycerols levels associated with an increase in the fecal excretion. No difference in blood cholesterol was seen at the sixth week of experiment. At the eighth week of experiment, there was a modest but significant reduction of serum total and high density lipoprotein (HDL) cholesterol in apoE(-/-) mice fed on gel diet compared to the control. Total cholesterol/HDL cholesterol ratio was 2-fold higher in the gel group than that seen in the control group (14.39 and 7.84, respectively). Histological analyzes showed a 2.2-fold increase in the dimension of the atherosclerotic plaques in the proximal aorta in apoE(-/-) mice fed on a gel diet compared to those fed on a control diet. The gel diet also promoted a reduction in the fecal excretion of bile acids. Hepatic cholesterol was similar in both groups. In conclusion, although gelatin reduced total serum cholesterol, this reduction was associated to a decrease of HDL cholesterol and consequent increase of total cholesterol/HDL cholesterol ratio, resulting in an acceleration of atherogenesis.     

Serum cholestanol and plant sterol levels in relation to cholesterol metabolism in middle-aged men

Serum cholestanol was studied in relation to fecal cholestanol excretion and cholesterol metabolism in a random middle-aged population of 61 men. The serum concentrations of cholestanol ranged from 1.6 to 10.8 mumol/L and were positively correlated with those of serum total LDL and HDL cholesterol. In terms of millimole per mole of cholesterol, these correlations disappeared; inverse associations were found with VLDL cholesterol and triglyceride levels, the P/S ratio of dietary fat, and the amount of fecal plant sterols, but not with fecal cholestanol. The serum contents of cholestanol (1) were also closely positively associated with those of serum plant sterols (campesterol and sitosterol) and fractional cholesterol absorption, (2) were inversely related to the fecal excretion of neutral sterols and cholesterol synthesis which were measured either by the sterol balance technique or serum cholesterol precursor sterols (desmosterol and lathosterol), and (3) were unrelated to bile acid synthesis. Fecal cholestanol (mean = 12.5 mg/d) was (1) clearly higher than the dietary cholestanol intake (less than 2 mg/d), (2) unrelated to serum cholestanol, and (3) positively correlated with the intestinal cholesterol (dietary plus endogenous) flux as well as fecal plant sterols, neutral sterols, and bacterial products of cholesterol. The study emphasizes that, in normal men, high serum cholestanol levels reflect high efficiency of intestinal sterol absorption and low cholesterol synthesis. Thus, the changes in the serum contents of cholestanol are parallel with those of plant sterols and opposite to those of cholesterol precursor sterols.     

Casein-induced hypercholesterolemia in rabbits: distribution of cholesterol, triglycerides and phospholipids between serum and liver

Replacement of soy protein by casein in the cholesterol-free, semipurified diet of rabbits caused hypercholesterolemia within 7 days. After 36 days, the serum of casein-fed rabbits displayed elevated levels of free and esterified cholesterol and phospholipids, but not of triglycerides. Most of the excess of serum cholesterol in the casein group was localized in the LDL fraction, but there were marked variations in the density profile of the serum lipoproteins between individual rabbits. Dietary casein induced an increased content in liver of free and esterified cholesterol, but not of phospholipids and triglycerides. The molar ratio of free to esterified cholesterol in the liver was decreased by casein. In contrast, feeding casein resulted in an increase of this ratio in the serum.     

Substitution of mixed amino acids resembling soy protein for mixed amino acids resembling casein in the diet reduces plasma cholesterol in slowly,but not rapidly fed nor fasted baboons

Studies of cholesterol and triglyceride metabolism were conducted under steady-state conditions in conscious restrained female baboons to ascertain (1) whether the cholesterol- and triglyceride-lowering effects of soy protein v casein in nonrodents can be explained by differences in amino acid composition between the two proteins and (2) whether the lipid-lowering effects of soy protein are influenced by fasting or the rate of feeding, ie, the nutritional state. The metabolic changes underlying the changes in serum cholesterol and triglyceride concentration were also investigated. Isocaloric diets consisting of 45% mixed amino acids (soy or casein type), 50% glucose and 5% corn oil, including all nutritional requirements, were infused intraduodenally for five days. There were no differences in lipid levels between the soy and casein diets in fasting baboons (days 4 or 5) or when the daily diet (calculated to equal 24 hours of energy utilization) was given rapidly by constant intraduodenal infusion over seven hours (day 4). During rapid feeding there was, unexpectedly, no significant change in plasma cholesterol concentration, but the estimated rate of cholesterol oxidation to bile acids fell significantly by 38 ± 6% (from 39 ± 4 to 24 ± 3 mg/d). Significant differences between the soy and casein diets were observed only in the fed state produced by the slow constant isocaloric intraduodenal infusions of the diets [5.8 mg mixed amino acids (soy or casein type) plus 7.2 mg glucose/min/kg body wt^0.75] on day 5. These diets were calculated to equal the simultaneous rate of energy utilization. During the slow (eight to ten hour) infusions the decrease in plasma cholesterol concentration was significantly greater with the soy v casein diet (25 ± 6 v 12 ± 4%, P < .02). Likewise, with the soy diet there was a reduction of serum triglycerides in 7 of 9 experiments (.05 < P < .10), which could be explained, at least in part, by a significant reduction in plasma VLDL triglyceride secretion (0.8 ± 0.2 v 1.4 ± 2 μmol TGFA/min/kg body wt^0.75, P < .005). Thus, both the nutritional status of the animals (fed or fasting) and the rate of feeding (rapidly or slowly at the calculated simultaneous rate of energy utilization) had a profound influence on the differential cholesterol- and triglyceride-lowering effects of soy protein v casein type diets. This explains the dissociation of the postprandial hypocholesterolemic effect of the soy type diet from its tendency to even elevate fasting cholesterol levels. These studies demonstrate the crucial importance of testing therapeutic diets under various nutritional conditions and of selecting an appropriate experimental model which allows for rigorous dietary control.     

Daily elimination of fecal neutral sterols by humans.

A study was made of the daily elimination of fetal neutral sterols in 22 healthy subjects and the average proportions of the main sterols were established. These were cholesterol (9.5%), its main bacterial transformation products: coprostanol (65%) and coprostanone (less than 6%), cholestanol (less than 2%), delta7-cholestenol (less than 2%) and phytosterols (18%). Epicoprostanol, which indicates a secondary mean of bacterial degradation of cholesterol has been searched for systematically. In general, traces only are present but in one case it amounts to more than 8% of the neutral sterols. The bulk of neutral sterols eliminated daily is very variable for different subjects and also for a same subject, although the concentration of fecal sterols is relatively constant (6.37 +/- 0.36 mg of sterols/g of feces). For a given subject under controlled diet conditions, differences in fecal elimination of sterols can essentially be ascribed to irregularity of digestive transit.