Fecal Steroid Excretion Research Articles

コレステロール無添加飼料時のラット脂質代謝に及ぼす改質ビート食物繊維の影響

The effect of the physical properties of beet dietary fiber (BDF) on lipid metabolism was examined in rats fed a cholesterol-free diet containing 25%casein for 12 weeks. We prepared three kinds of BDF with different particle sizes (16-32, 60-80, and 150-250 mesh). When rats were fed the smaller BDFs, the cecal organic acid content was higher. All three kinds of BDF prevented elevation of serum cholesterol and triglyceride concentrations, and also decreased liver total lipids. The smallest BDF tended to depress the serum cholesterol concentration more than the two other BDFs, there were no differences depending on particle size in the effects on the triglyceride concentration. We prepared a chemically modified BDF(m-BDF)by glyoxal treatment and a colloidal BDF (c-BDF) by passage of BDF through a ceramic grinder. BDF and c-BDF depressed serum cholesterol and triglyceride concentrations, but m-BDF had no such effect. These results suggest that there is a relationship between fermentability and the hypolipidemic activity of BDF. The hypolipidemic activity of BDF was not related to fecal excretion of steroids.

Reduction of hypercholesterolemia and proteinuria in nephritic rats by low-meat-protein diets.

The effects of low-meat-protein diets on hypercholesterolemia and proteinuria were studied in rats with nephrotoxic serum nephritis. After an injection of nephrotoxic serum, rats were given either a 20% meat-protein diet (20M), an 8.5%-meat-protein diet (8.5M), or a valine-(0.05%)-supplemented 8.5%-meat-protein diet (8.5MV) for 12 days. Urinary protein excreted from the 20M-fed, nephritic control rats increased rapidly and linearly during the initial 3 days, and thereafter the high excretion rate was maintained for up to 12 days. Two low-meat-protein diets (8.5M, 8.5MV) commenced to suppress proteinuria 3 days after feeding and the suppression was preserved during the rest of the experimental periods. Compared with the 20M, both low-meat-protein diets significantly improved hypercholesterolemia induced in this nephritic model. These two diets significantly enhanced the fecal excretion of neutral sterols. They caused neither fatty liver nor severe growth retardation. These effects of 8.5MV were identical to those of 8.5M. The results suggest that low-meat-protein feeding, without amino acid supplementation, improves hypercholesterolemia and proteinuria in nephritis without severe protein malnutrition. The results also suggest that the hypocholesterolemic effect of the low-meat-protein diets may be, at least in part, attributed to increased fecal excretion of steroids.

Fat Containing Stearic Acid Increases Fecal Neutral Steroid Excretion and Catabolism of Low Density Lipoproteins Without Affecting Plasma Cholesterol Concentration in Hamsters Fed a Cholesterol-Containing Diet

To examine the effect of different saturated fatty acids on the dietary cholesterol-induced elevation of serum cholesterol concentration and suppression of LDL catabolism, for 4 wk hamsters were fed purified diets containing 8% purified fats in which saturated fatty acids, lauric, myristic, palmitic and stearic acids were the sole variable. The dietary fat was composed of 50% saturated fatty acid, 30% oleic acid and 20% linoleic acid (polyunsaturated:saturated = 0.4). In hamsters fed the cholesterol-containing diet, fat containing stearic acid, compared with the fats containing other saturated fatty acids resulted in greater fractional catabolic rate of [125I]-labeled homologous LDL, greater fecal excretion of neutral steroids and lower liver cholesterol concentration, although the elevation of serum cholesterol concentration due to consuming a cholesterol-containing diet was not ameliorated. Stearic acid fat resulted in greater excretion of fecal fatty acids and lower apparent absorption of the dietary fats in hamsters fed diets with and without cholesterol. In hamsters fed the cholesterol-free diets, type of dietary fat did not affect the fractional catabolic rate of LDL, although stearic acid fat resulted in greater fecal neutral steroid excretion and lower serum and liver cholesterol concentrations. These observations suggested that purified fat containing stearic acid results in lower plasma cholesterol concentration in hamsters via stimulation of neutral steroid excretion, but addition of cholesterol to the diets obscures this effect.

Comparative effects of four legume species on plasma lipids and faecal steroid excretion in hypercholesterolaemic pigs

The effect of four species of legume seeds on plasma cholesterol levels and faecal steroid excretion was studied in pigs. Thirty-six growing boars were randomly allocated in groups of six to six diets which they ate continuously for 42 d. The diets fed were: 1, a semi-purified (SP; control group 1) diet; 2, SP + 10 g cholesterol/kg (control group 2); 3, 4, 5, 6, SP + cooked legumes (70:30, w/w; respectively baked beans (Phaseolus vulgaris), peas (Pisum sativum), lentils (Lens culinaris Medik.), butter beans (Phaseolus lunatus)) + 10 g cholesterol/kg. Fasting blood samples were taken on days 0, 14, 28, and 42 for the determination of total plasma cholesterol, high-density-lipoprotein (HDL)-cholesterol and triacylglycerols. Between days 7 and 11 and days 28 and 32 complete 5 d faecal collections were made for the measurement of neutral, acidic and conjugated steroids. After 42 d total cholesterol and HDL-cholesterol levels were raised significantly in all groups, but to different extents. In comparison with control group 2, diet-induced hypercholesterolaemia was significantly inhibited in the groups consuming baked beans, peas and butter beans, although HDL-cholesterol levels were maintained. Faecal steroid excretion by the legume groups was not significantly different from that of control group 2. The results suggest that the mechanism for the hypocholesterolaemic effect does not involve increased hepatic bile acid synthesis and thereby increased cholesterol clearance via the intestinal route.

Effects of chitosan hydrolyzates on lipid absorption and on serum and liver lipid concentration in rats

The enzymatic hydrolysates of chitosan with average molecular weights range from 5000 to 20000 and with low viscosity interfered with intestinal absorption of cholesterol in lymph fistulated rats and increased fecal excretion of neutral steroids in rats fed a cholesterol-enriched diet. The hydrolysates exerted a cholesterol-lowering activity, and it was more marked in the liver than in the serum. They also reduced liver triglyceride significantly. Chitosan hydrolysates with average molecular weights of 10000-20000 were as effective as high-viscous chitosan with a molecular weight of 50000. The results indicate usability of low-viscosity chitosan hydrolysate as a hypocholesterolemic agent.

Effects of dietary fibre on faecal steroid measurements in baboons (Papio cynocephalus cynocephalus).

A study was conducted in captive baboons to determine (i) the impact of cereal dietary fibre on faecal progestogen excretion, and (ii) whether means of controlling dietary effects could be identified. Blood was collected on 3 days per week and faeces on 5 days per week from four unanesthetized cyclic female baboons, consecutively fed three diets of 5, 10 and 20% fibre for 90 days per diet. A 2 day lag time was detected before progesterone in the blood appeared in the faeces, regardless of diet (mean correlation was 0.62, P = 0.002). Increased dietary fibre had a negative effect on progestogen excretion (P < 0.004). Correspondence between blood and faecal progestogens was consistently greatest and the effect of dietary fibre least when faecal progestogens were expressed g-1 dry faeces. Several means of indexing faecal steroid excretion rates were examined including dehydroepiandrosterone (DHEA) and a number of byproducts of cholesterol metabolism. The cholesterol metabolite, cholestanone, was positively correlated with dietary fibre (r = 0.27; P < 0.04). Multiplying faecal progestogen concentration by the cholestanone g-1 dry faeces concentration increased the correlation between serum and cholestanone-indexed faecal progestogens (r = 0.78, P = 0.0001) compared with nonindexed progestogens (r = 0.71, P = 0.0001). We conclude that expressing faecal progestogens g-1 dry faeces may be sufficient and the most cost-effective method for controlling for most dietary effects when the objective is monitoring longitudinal endocrine status in baboons. However, it may be appropriate to express faecal progestogens by cholestanone concentrations when increased precision is needed to overcome the effects of profound variations in dietary fibre.

Combined effects of dietary protein and fat on lipid metabolism in rats.

The combined effects of dietary protein (casein, whey protein, or soy protein) and fat (safflower oil, perilla seed oil, or their mixed oil; linoleic acid/alpha-linolenic acid = 5.0) on several lipid parameters were studied in rats. Serum cholesterol and triglyceride levels were lower in perilla seed oil groups irrespective of the protein sources. Liver triglyceride level, and fecal excretion of steroids were influenced mainly by protein sources, particularly isolated soy protein lowered liver triglyceride level, and increased the fecal steroid excretion. The fatty acid composition of liver phosphatidylcholine was influenced by dietary fat sources. The proportion of arachidonic acid was significantly lower in rats fed perilla seed oil than in those fed safflower oil or mixed oil, while the proportion of eicosapentaenoic acid was higher in rats fed perilla seed oil than in those fed safflower oil. Arachidonic acid/linoleic acid ratio was significantly lower in perilla seed oil groups, and tended to be higher in casein groups. Eicosapentaenoic acid/arachidonic acid ratio was influenced by both dietary protein and fat, and protein-fat interaction was observed. Eicosapentaenoic acid/arachidonic acid ratio was higher in perilla seed oil groups, and isolated soy protein in perilla seed oil groups lowered the ratio in comparison with other protein sources in perilla seed oil groups.

Effects of Different Triglyceride Saturated Fatty Acids on Tissue Lipid Level, Fatty Acid Composition, Fecal Steroid Excretion, Prostacyclin Production, and Platelet Aggregation in Rats.

Male Sprague-Dawley rats were fed for 3 weeks cholesterol-enriched diets containing 7% interesterified fats in which saturated fatty acids, lauric, myristic, palmitic, and stearic acids, were the sole variable. The dietary fat was composed of 50% saturated fatty acid, 30% oleic acid, 14% linoleic acid, and 6% α-Iinolenic acid (P/S =0.4, n-6/n-3 =2.3). There was no difference in food intake, body weight gain, or liver and epididymal adipose tissue weight among the groups, although the apparent fatty acid absorption decreased with increasing chain-length of dietary saturated fatty acids. Plasma lipid levels were comparable among the groups, but the concentration of liver cholesterol was significantly lower, and fecal excretion of neutral but not acidic steroids was significantly higher in the stearic acid group even compared with the palmitic acid group. The liver triglyceride decreased upon feeding palmitic or stearic acid fats. The fatty acid composition of adipose tissue but not liver triglyceride apparently reflected the source of dietary fats, but a considerable portion of stearic acid appeared to be desaturated to oleic acid. The proportion of arachidonic acid in plasma cholesterol ester and that of linoleic acid in liver phosphatidylethanolamine decreased with the chain-length of saturated fatty acids. The stearic acid-fat significantly reduced platelet aggegation by ADP and aortic production of prostacyclin, and there was a similar but to a less marked response pattern in the palmitic acid-fat. These observations suggest that the different saturated fatty acids exert differential effects on various lipid parameters.

The effect of various phospholipids on plasma lipoproteins and liver lipids in hypercholesterolemic rats.

Rats were fed a hypercholesterolemic diet (5% lard, 0.5% cholesterol, and 0.25% sodium cholate) containing 5% of dietary phospholipid as safflower phospholipid (SAP), soybean phospholipid (SOP), or egg yolk phospholipid (EGP), or 5% of soybean oil (SO) as a control for 4 weeks. The concentrations of plasma cholesterol were significantly higher in rats fed the EGP diet than those of the other diets. Similarly, the concentrations of chylomicron plus very low density lipoprotein (VLDL) cholesterol were higher in rats fed the EGP diet. The phospholipid diets induced a significant increase of high density lipoprotein (HDL) cholesterol in comparison with the SO diet. The concentrations of liver cholesterol were significantly lower in rats fed the phospholipid diets than those of the SO diet. Among phospholipid-fed rats, the SAP and SOP diets decreased the concentrations of liver cholesterol compared with the EGP diet. The activity of plasma lecithin-cholesterol acyltransferase (LCAT) was significantly increased in rats fed the phospholipid diets. The phospholipid diets caused an enhanced excretion of neutral steroids into feces. Among phospholipid-fed rats, the SAP and SOP diets increased the excretion of fecal neutral steroids compared with the EGP diet. The fatty acid composition of HDL phospholipid was slightly reflected by the major dietary fat source. These results suggest that SAP and SOP inhibit markedly the absorption of dietary cholesterol in the small intestine of hypercholesterolemic rats and that the effect of SAP and SOP on plasma cholesterol metabolism may be different from that of EGP.

Effects of different saturated fats on various aspects of lipid metabolism in rats hypersensitive to dietary cholesterol

Effects of palm oil (PO) and coconut oil (CO) mixed with corn on lipid metabolism were compared with those of lard in rats hypersensitive to dietary cholesterol. Rats were fed one of four cholesterol-enriched diets containing different dietary fats, equiweight mixtures of either soybean oil-lard or soybean oil-lard-PO-CO, at about 26 or 42 energy % levels. The concentration of serum cholesterol did not increase when polyunsaturated fat was replaced with saturated fat of plant origin, and it tended to be lower with an increase in the dietary fat level. In addition, the PO-CO mixture reduced the liver cholesterol concentration at both energy levels compared with lard. There was no fat-dependent difference in fecal steroid excretion and the fatty acid composition of serum and liver phospholipids. Zymosan injection caused a reduction of serum triglyceride in the PO-CO group and a reduction of liver cholesterol in the lard group. The elevation of serum cholesterol and the reduction of liver triglyceride upon injection of zymosan were independent of the source of dietary saturated fats. Thus, PO and CO in combination may specifically modulate lipid metabolism under the immunologically stimulated as well as non-stimulated situations.

Hypocholesterolemic Effect of Undigested Fraction of Soybean Protein in Rats Fed No Cholesterol

The hypocholesterolemic activity of the undigested fraction (UDF) from soybean protein was significantly greater than that of the parent protein even when rats were fed no cholesterol. This fraction prevented the rise of serum cholesterol during a feeding period of 4 months. There was a gradual decrease in serum cholesterol as the proportion of UDF in the casein diet was increased, and 50% replacement produced much reduction. Liver cholesterol and triglyceride also decreased. Compared with the results obtained with soybean protein, UDF increased fecal excretion of both neutral and acidic steroids, suggesting a possible mechanism for its hypocholesterolemic effect. UDF seemed to interfere with the metabolism of linoleic acid to arachidonic acid more than soyben protein, which reduced desaturation more than casein did. The results showed that UDF was hypocholesterolemic when the diet was cholesterol-free, and that the effect on linoleic acid metabolism was specific.

Cholesterol metabolism in distance runners.

Faecal steroid excretion, including betasitosterol excretion, whole-body cholesterol synthesis, plasma lipids, and lipoprotein concentrations and habitual diet, were determined in 14 male distance runners and 14 sedentary men. The proportion of cholesterol-derived steroids excreted as bile acids, and the quantity of betasitosterol excreted in the faeces were significantly (P less than 0.05) higher in the runners compared with the sedentary men. Faecal betasitosterol excretion and the proportion of cholesterol-derived steroids excreted as bile acids were correlated significantly in the distance runners and the sedentary men (r = 0.774, n = 28, P less than 0.001). These results suggest that greater dietary intake of plant sterols may contribute to the higher proportion of cholesterol-derived steroids excreted as bile acids in distance runners.

Sluggish sitosterol turnover and hepatic failure to excrete sitosterol into bile cause expansion of body pool of sitosterol in patients with sitosterolemia and xanthomatosis.

Sitosterolemia and xanthomatosis are characterized by the development of tendon and tuberous xanthomas at an early age and premature atherosclerosis despite normal plasma cholesterol concentrations. The reason(s) for the xanthoma formation and premature atherosclerosis are not clearly understood. The accumulation of sitosterol in the tissues of these patients could be due to increased uptake of low density lipoprotein (LDL) via LDL receptors because of an expanded sitosterol pool caused by sluggish turnover and decreased excretion of sitosterol into bile and feces coupled with the hyperabsorption of sitosterol. We have studied sitosterol and cholesterol turnovers, the biliary and fecal excretion of neutral and acidic steroids, and the response of plasma sterol (sitosterol and cholesterol) levels to either a sterol-free formula or low plant sterol diet in three patients. The average half-life of the first exponential (tA1/2) for sitosterol was 9.2 +/- 3.3 (mean +/- SD) days, which was more than twice that in normal humans. The second exponential (tB1/2) was 156 +/- 108 days, which was nearly 10 times longer than that for normal humans. The average cholesterol production rate in pool A was 0.87 g/day, which is about 40% of that in normal humans. Cholesterol synthesis measured by the sterol balance technique was also found to be about 70% lower than that for normal humans. In two patients fed a sterol-free formula diet, by 25 days their plasma sitosterol and cholesterol levels had decreased by 42% and 36%, respectively. However, in one patient plasma sitosterol and cholesterol concentrations remained unchanged while on the low plant sterol-mixed food diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypocholesterolemic action of dietary phosphatidylethanolamine in rats sensitive to exogenous cholesterol

Supplementation of phosphatidylethanolamine (PE) to the cholesterol-free diet decreases the serum cholesterol level in rats. The base portion of PE is responsible for this action, but its mechanism is not clarified yet. As an initial step to understand this mechanism, some of the metabolites of the ethanolamine portion of dietary PE in the liver and blood plasma were determined in the present study by using hypercholesterolemic rats sensitive to exogenous cholesterol. The rats were fed the purified diet containing 1% cholesterol, and either PE or phosphatidylcholine (PC) as a control at 2% level each for 2 weeks. The magnitude of an elevation of the serum cholesterylester level was lower in rats fed PE than in those fed PC. The hepatic levels of triglyceride and cholesterylester tended to be higher in rats fed PE. Fecal steroid excretion was not influenced by the type of the dietary phospholipids. The level of serum ethanolamine and liver phosphoethanolamine was 1.5- and 5.8-fold higher, respectively, in rats fed PE than in those fed PC. The concentration of serum PC was lower and that of the PE was higher in rats fed PE. The level of liver phosphoethanolamine was correlated inversely to that of serum cholesterylester in rats given PE. From these results, it is suggested that inadequate utilization of PC for a component of secretory lipoproteins in the liver and for a substrate donor for cholesterylester formation in the blood serum may be relevant to the cholesterol-lowering action of the dietary PE.

Effects of dietary sulfur amino acids and glycine on fecal steroid excretion in hepatoma-bearing rats.

Effects of dietary sulfur amino acids and glycine on fecal steroid excretion in hepatoma-bearing rats.

Activities of hepatic rate-limiting enzymes in cholesterol biosynthesis and degradation in rats fed desalted miso.

Effect of dietary miso on the activities of various hepatic enzymes in lipid biosynthesis and degradation was examined in rats fed a cholesterol-free diet for 18 days. The inclusion of 20% desalted miso to the experimental diet significantly decreased the concentration of serum cholesterol and doubled the fecal excretion of acidic steroids without influencing that of neutral steroids. The dietary miso greatly increased the activities of the rate-limiting enzymes in cholesterol biosynthesis and degradation in liver microsomes. In contrast, dietary miso was ineffective in modulating activities of enzymes in fatty acid oxidation and glycerolipid synthesis. Microsomal lipid contents and compositions were uninfluenced by dietary miso. It was suggested that the miso contained the component (s) which specifically increase the facal excretion of bile acids. The enhanced bile acid excretion may be compensated by the increase in the catabolism of cholesterol to bile acids and reduce the serum cholesterol concentration as observed in the present study.

Dietary cholesterol absorption, and sterol and bile acid excretion in hypercholesterolemia-resistant white rabbits.

The New Zealand white (NZW) rabbit fed a 0.1% cholesterol-enriched diet (CD) typically responds (normoresponsive, NR) by quickly developing hypercholesterolemia. To study the underlying mechanisms responsible for the widespread phenomenon of inter-individual variability of response to dietary cholesterol, a unique hypercholesterolemia-resistant (RT) rabbit model was developed. These animals were utilized to investigate selected potential mechanisms that might enable the RT animal to compensate for dietary cholesterol overload. When rabbits were fed the low-cholesterol stock diet, there was no significant difference in the plasma cholesterol concentrations of the NR and the RT animals. However, a significant rise was observed in the NR rabbits within 1 month of their being placed on the cholesterol-enriched diet; the plasma cholesterol concentration of the RT animals was not affected. During consumption of the cholesterol diet the cholesterol absorption rate was somewhat greater in the NR rabbits (P less than 0.05), whereas intestinal transit times and the fecal excretion of neutral steroids were substantially the same in both groups. In contrast, the fecal bile acid excretion of the RT animals was more than twice as great (P less than 0.0001) as that of the NR animals. We conclude that the response to dietary cholesterol is a heritable trait in these rabbits and that, although less dietary cholesterol was absorbed by the RT animals, it appears that a major mechanism controlling plasma cholesterol levels involves the rate of conversion of cholesterol to bile acids and their subsequent excretion.

Effects of Excess Dietary Tyrosine on Cholesterol, Bile Acid Metabolism and Mixed-Function Oxidase System in Rats

Excess dietary tyrosine (12%) caused hypercholesterolemia in male Wistar rats and significantly increased cytochrome P-450 and b5 contents. Bile flow and biliary output of total bile acids were significantly increased in rats fed this diet. Biliary output of cholesterol was not significantly altered, whereas that of taurocholic acid was significantly increased. Excess dietary tyrosine significantly decreased the fecal excretion of neutral steroids, whereas total steroid excretion was not significantly changed. The present results indicate that excess dietary tyrosine causes hypercholesterolemia without modifying the fecal total steroid excretion, thus supporting our previous hypothesis that stimulated synthesis of cholesterol is a main reason why excess dietary tyrosine leads to hypercholesterolemia.

Influence of peanut oil of different origins on lipid metabolism in rats

Mechanism(s) underlying the unexpected atherogenicity of peanut oil are obscure. Triglyceride structure and/or composition may contribute to atherogenicity. The studies reported here were designed to explore further effects on lipid metabolism. We have compared in rats the effects on lipid metabolism of: corn oil (CO), commercial peanut oil (PNO), randomized PNO (PNOR), and oils prepared from two specific cultivars of peanut, India White (IW) and Jenkins Jumbo (JJ). The oils (15%) were fed for 3 weeks in a semipurified diet. There were no differences in weight gain, liver weight, or serum lipids. Liver cholesterol levels were not significantly different, but liver triglycerides were lower in rats fed IW or JJ. Feces were collected at 10 and 20 days. Fecal fat (%) was similar in all groups. All rats excreted increasing amounts of 16:0 and 18:0, but less 18:1 and 18:2, suggesting conservation of the more unsaturated fatty acids. Fecal excretion of neutral steroids was similar in the five dietary groups, but acidic steroid excretion was lower in rats fed CO and PNO than in the other groups. Triglyceride content of the intestinal mucosa differed significantly, being (mg/g): CO −10.8±1.7; PNO-19.15±1.6; PNOR-10.5±1.8;IW-17.6±1.8; and JJ-14.6±0.9. In every group, mucosal 18:1/18:2 was higher than that of CO fed. Retention of triglycerides in the mucosa may be related to atherogenic effects.

Cholesterol-Lowering Activity of Various Undigested Fractions of Soybean Protein in Rats

The undigested high-molecular-weight fraction (HMF) of soybean protein prepared after exhaustive digestion by microbial proteases significantly decreased serum cholesterol levels to approximately 45% (p less than 0.05) of those observed with the parent protein in rats fed diets containing cholesterol (0.5%) and sodium cholate (0.125%). HMF bound conjugated bile salts in vitro and significantly increased fecal excretion of both neutral and acidic steroids by 65-95% and 80-170% more, respectively (p less than 0.05), than did the intact protein. Extraction of HMF with methanol slightly decreased the activity, but the methanol-soluble fraction was not regarded as a principal determinant. Soybean saponin at the dietary level equivalent to that contained in HMF did not effectively lower serum cholesterol. The activity was not necessarily duplicated even when methanol-treated fractions were recombined. Further degradation of the methanol-extracted HMF by various proteases resulted in loss of activity. HMF obtained after pepsin digestion exerted a potential similar to that of HMF prepared after digestion by microbial proteases.