Impact of β-cyclodextrin and resistant starch on bile acid metabolism and fecal steroid excretion in regard to their hypolipidemic action in hamsters1

To examine the impact on bile acid metabolism and fecal steroid excretion as a mechanism involved in the lipid-lowering action of β-cyclodextrin and resistant starch in comparison to cholestyramine, male golden Syrian hamsters were fed 0% (control), 8% or 12% of β-cyclodextrin or resistant starch or 1% cholestyramine. Resistant starch, β-cyclodextrin and cholestyramine significantly lowered plasma total cholesterol and triacylglycerol concentrations compared to control. Distinct changes in the bile acid profile of gallbladder bile were caused by resistant starch, β-cyclodextrin and cholestyramine. While cholestyramine significantly reduced chenodeoxycholate independently of its taurine–glycine conjugation, β-cyclodextrin and resistant starch decreased especially the percentage of taurochenodeoxycholate by ?75% and ?44%, respectively. As a result, the cholate:chenodeoxycholate ratio was significantly increased by 100% with β-cyclodextrin and by 550% with cholestyramine while resistant starch revealed no effect on this ratio. β-Cyclodextrin and resistant starch, not cholestyramine, significantly increased the glycine:taurine conjugation ratio demonstrating the predominance of glycine conjugated bile acids. Daily fecal excretion of bile acids was 4-times higher with 8% β-cyclodextrin and 19-times with 1% cholestyramine compared to control. β-Cyclodextrin and cholestyramine also induced a 2-fold increase in fecal neutral sterol excretion, demonstrating the sterol binding capacity of these two compounds. Resistant starch had only a modest effect on fecal bile acid excretion (80% increase) and no effect on excretion of neutral sterols, suggesting a weak interaction with intestinal steroid absorption. These data demonstrate the lipid-lowering potential of β-cyclodextrin and resistant starch. An impaired reabsorption of circulating bile acids and intestinal cholesterol absorption leading to an increase in fecal bile acid and neutral sterol excretion is most likely the primary mechanism responsible for the lipid-lowering action of β-cyclodextrin. In contrast, other mechanisms involving the alterations in the biliary bile acid profile or repressed hepatic lipogenesis, e.g., VLDL production, appear to be involved in the hypolipidemic effect of resistant starch.     

Cholesterol catabolism in the rabbit in fasted and fed states.

Urinary and fecal endogenous steroid excretion of fed or fasted New Zealand white rabbits was determined by the isotopic steady state method after subcutaneous implantation of radioactive cholesterol. While plasma cholesterol was increasing during a 9-day fast, fecal steroid excretion decreased to 10% of the excretion rates in the fed state. Refeeding the fasted rabbits led to a decrease in plasma cholesterol and an increase in fecal endogenous steroid excretion. Urinary steroid excretion, which represented 18% of total endogenous steroid excretion for fed animals, decreased during fasting and increased during refeeding, but these changes were relatively small. The small intestine, cecum, and colon of fed or fasted rabbits had similar endogenous steroid was acidic steroid. During attempts to alter the circulating bile acid concentration by supplying deoxycholate (200 mg/day) to fed rabbits or cholestyramine (2 g/day) to fasted rabbits, plasma cholesterol concentration did not change to the same extent as during fasting or refeeding, respectively. The decreased cholesterol catabolism and the hypercholesterolemia that are seen in the fasting rabbit may result from decreased clearance of plasma cholesterol.     

Effect of diosgenin on lipid metabolism in rats.

The purpose of this study was to determine whether diosgenin suppresses cholesterol absorption in rats, and to examine relevant changes in cholesterol and bile acid metabolism. Diosgenin fed with the diet for 1 week inhibited cholesterol absorption as determined by the serum isotope ratio technique, as well as by measuring in the feces the amount of unabsorbed radioactivity from orally administered [3H]cholesterol. In addition, diosgenin suppressed the serum and liver uptake of radioactivity from co-administered [3H]cholesterol as well as the accumulation of liver cholesterol in the cholesterol-fed rat; diosgenin was substantially more active than cholestyramine or beta-sitosterol. In vitro, diosgenin had no effect on the activity of rat pancreatic esterase. Diosgenin decreased the elevated cholesterol in serum LDL and elevated cholesterol in the HDL fraction of cholesterol-fed rats; diosgenin had no effect on serum cholesterol in normocholesterolemic rats. In contrast to cholestyramine, diosgenin markedly increased neutral sterol excretion without altering bile acid excretion; in vitro, diosgenin had no effect on bile acid binding. Diosgenin treatment increased hepatic and intestinal cholesterol synthesis as well as the activity of hepatic HMG CoA reductase. This was accompanied by increased biliary concentration of cholesterol, but not of bile acids. Diosgenin had no effect on cholesterol synthesis when added to normal rat liver homogenates. It was concluded that diosgenin interferes with the absorption of cholesterol of both exogenous and endogenous origin; such interference is accompanied by derepressed, i.e., increased, rates of hepatic and intestinal cholesterol synthesis. The increased unabsorbed cholesterol together with enhanced secretion of cholesterol into bile resulted in increased excretion of neutral sterols without affecting the biliary and fecal excretion of bile acids.     

Antilithiasic effect of beta-cyclodextrin in LPN hamster: comparison with cholestyramine

Beta-Cyclodextrin (BCD), a cyclic oligosaccharide that binds cholesterol and bile acids in vitro, has been previously shown to be an effective plasma cholesterol lowering agent in hamsters and domestic pigs. This study examined the effects of BCD as compared with cholestyramine on cholesterol and bile acid metabolism in the LPN hamster model model for cholesterol gallstones. The incidence of cholesterol gallstones was 65% in LPN hamsters fed the lithogenic diet, but decreased linearly with increasing amounts of BCD in the diet to be nil at a dose of 10% BCD. In gallbladder bile, cholesterol, phospholipid and chenodeoxycholate concentrations, hydrophobic and lithogenic indices were all significantly decreased by 10% BCD. Increases in bile acid synthesis (+110%), sterol 27-hydroxylase activity (+106%), and biliary cholate secretion (+140%) were also observed, whereas the biliary secretion of chenodeoxycholate decreased (-43%). The fecal output of chenodeoxycholate and cholate (plus derivatives) was increased by +147 and +64%, respectively, suggesting that BCD reduced the chenodeoxycholate intestinal absorption preferentially. Dietary cholestyramine decreased biliary bile acid concentration and secretion, but dramatically increased the fecal excretion of chenodeoxycholate and cholate plus their derivatives (+328 and +1940%, respectively). In contrast to BCD, the resin increased the lithogenic index in bile, induced black gallstones in 34% of hamsters, and stimulated markedly the activities of HMG-CoA reductase (+670%), sterol 27-hydroxylase (+310%), and cholesterol 7alpha-hydroxylase (+390%). Thus, beta-cyclodextrin (BCD) prevented cholesterol gallstone formation by decreasing specifically the reabsorption of chenodeoxycholate, stimulating its biosynthesis and favoring its fecal elimination. BCD had a milder effect on lipid metabolism than cholestyramine and does not predispose animals to black gallstones as cholestyramine does in this animal model.     

Soyasaponins lowered plasma cholesterol and increased fecal bile acids in female golden Syrian hamsters

A study was conducted in hamsters to determine if group B soyasaponins improve plasma cholesterol status by increasing the excretion of fecal bile acids and neutral sterols, to identify group B soyasaponin metabolites, and to investigate the relationship between a fecal group B soyasaponin metabolite and plasma lipids. Twenty female golden Syrian hamsters, 11-12 weeks old and 85-125 g, were randomly assigned to a control diet or a similar diet containing group B soyasaponins (containing no isoflavones), 2.2 mmol/kg, for 4 weeks. Hamsters fed group B soyasaponins had significantly lower plasma total cholesterol (by 20%), non-high-density lipoprotein (HDL) cholesterol (by 33%), and triglycerides (by 18%) compared with those fed casein (P < 0.05). The ratio of total cholesterol to HDL cholesterol was significantly lower (by 13%) in hamsters fed group B soyasaponins than in those fed casein (P < 0.05). The excretion of fecal bile acids and neutral sterols was significantly greater (by 105% and 85%, respectively) in soyasaponin-fed hamsters compared with those fed casein (P < 0.05). Compared with casein, group B soyasaponins lowered plasma total cholesterol levels and non-HDL cholesterol levels by a mechanism involving greater excretion of fecal bile acids and neutral sterols. Hamsters fed group B soyasaponins statistically clustered into two fecal soyasaponin metabolite-excretion phenotypes: high excreters (n = 3) and low excreters (n = 7). When high and low producers of this soyasaponin metabolite were compared for plasma cholesterol status, the high producers showed a significantly lower total-cholesterol-to-HDL-cholesterol ratio compared with the low producers (1.38 +/- 0.7 vs. 1.59 +/- 0.13; P < 0.03). Greater production of group B soyasaponin metabolite in hamsters was associated with better plasma cholesterol status, suggesting that gut microbial variation in soyasaponin metabolism may influence the health effects of group B soyasaponins.     

ACAT2 and ABCG5/G8 are both required for efficient cholesterol absorption in mice: evidence from thoracic lymph duct cannulation

The metabolic fate of newly absorbed cholesterol and phytosterol is orchestrated through adenosine triphosphate-binding cassette transporter G5 and G8 heterodimer (G5G8), and acyl CoA:cholesterol acyltransferase 2 (ACAT2). We hypothesized that intestinal G5G8 limits sterol absorption by reducing substrate availability for ACAT2 esterification and have attempted to define the roles of these two factors using gene deletion studies in mice. Male ACAT2(-/-), G5G8(-/-), ACAT2(-/-)G5G8(-/-) (DKO), and wild-type (WT) control mice were fed a diet with 20% of energy as palm oil and 0.2% (w/w) cholesterol. Sterol absorption efficiency was directly measured by monitoring the appearance of [(3)H]sitosterol and [(14)C]cholesterol tracers in lymph after thoracic lymph duct cannulation. The average percentage (± SEM) absorption of [(14)C]cholesterol after 8 h of lymph collection was 40.55 ± 0.76%, 19.41 ± 1.52%, 32.13 ± 1.60%, and 21.27 ± 1.35% for WT, ACAT2(-/-), G5G8(-/-), and DKO mice, respectively. [(3)H]sitosterol absorption was <2% in WT and ACAT2(-/-) mice, whereas it was up to 6.8% in G5G8(-/-) and DKO mice. G5G8(-/-) mice also produced chylomicrons with ～70% less cholesterol ester mass than WT mice. In contrast to expectations, the data demonstrated that the absence of G5G8 led to decreased intestinal cholesterol esterification and reduced cholesterol transport efficiency. Intestinal G5G8 appeared to limit the absorption of phytosterols; ACAT2 more efficiently esterified cholesterol than phytosterols. The data indicate that handling of sterols by the intestine involves both G5G8 and ACAT2 but that an additional factor (possibly Niemann-Pick C1-like 1) may be key in determining absorption efficiency.     

Intestinal cholesterol absorption in the chyluria model

Isotopic methods for the measurement of dietary cholesterol absorption were compared with the lymph cholesterol balance procedure in filarial chyluria patients. After a single intravenous injection of radioactive cholesterol, absorption was found to be 746 +/- 136 mg/day by method I, which is based upon the fecal endogenous neutral steroid mass measurement, and 471 +/- 135 mg/day by the simultaneously measured lymph/plasma ratio of cholesterol specific activity (dpm/mg). The corresponding value, determined as the difference between lymph cholesterol transport on a cholesterol-containing diet (1500 mg) and on a cholesterol-free diet, was 622 mg/day. When radioactive cholesterol (1487 mg/day) was fed daily to a second patient, absorption determined by isotopic fecal recovery (353 mg/day) matched that obtained by the lymph balance procedure (326 mg/day). Transudation of plasma cholesterol into the intestinal lymph, estimated by the single intravenous injection of radioactive beta-sitosterol, was independent of both the luminal content of plant sterols and the absorption of dietary cholesterol. The absorption of endogenous cholesterol was calculated by: 1) subtracting the cholesterol originating from plasma (transudation) together with the absorbed dietary cholesterol found in lymph from the total mass of cholesterol transported in lymph, and 2) the lymph balance method, i.e., after interrupting the endogenous cholesterol mucosal uptake by beta-sitosterol feeding (9 g/day) while on a cholesterol-free diet. Endogenous cholesterol was preferentially absorbed compared to dietary cholesterol, but there was no competition for absorption. The major portion of dietary cholesterol found in lymph was esterified, but esterification was not a prerequisite for absorption.     

Liver X receptor-mediated activation of reverse cholesterol transport from macrophages to feces in vivo requires ABCG5/G8

Liver X receptor (LXR) agonists increase both total fecal sterol excretion and macrophage-specific reverse cholesterol transport (RCT) in vivo. In this study, we assessed the effects of ABCG5/G8 deficiency as well as those of LXR agonist-induction of RCT from macrophages to feces in vivo. A [(3)H]cholesterol-labeled macrophage cell line was injected intraperitoneally into ABCG5/G8-deficient (G5/G8(-/-)), heterozygous (G5G8(+/-)), and wild-type G5/G8(+/+) mice. G5/G8(-/-)mice presented increased radiolabeled HDL-bound [(3)H]cholesterol 24 h after the label injection. However, the magnitude of macrophage-derived [(3)H]cholesterol in liver and feces did not differ between groups. A separate experiment was conducted in G5G8(+/+) and G5G8(-/-) mice treated with or without the LXR agonist T0901317. Treatment with T0901317 increased liver ABCG5/G8 expression, which was associated with a 2-fold increase in macrophage-derived [(3)H]cholesterol in feces of G5/G8(+/+) mice. However, T0901317 treatment had no effect on fecal [(3)H]cholesterol excretion in G5G8(-/-) mice. Additionally, LXR activation stimulated the fecal excretion of labeled cholesterol after an intravenous injection of HDL-[(3)H]cholesteryl oleate in G5/G8(+/+) mice, but failed to enhance fecal [(3)H]cholesterol in G5/G8(-/-) mice. Our data provide direct in vivo evidence of the crucial role of ABCG5 and ABCG8 in LXR-mediated induction of macrophage-specific RCT.     

Cholesterol gallstones in alloxan-diabetic mice

Normal and alloxan-diabetic male mice (Crj-ICR) were fed a diet containing 0.5% cholesterol for 5 and 10 weeks, and gallbladder bile was analyzed for cholesterol, phospholipids and bile acids, feces for sterols and bile acids, and plasma and liver for cholesterol, phospholipids, and triglycerides. Normal mice developed no gallstones but the diabetic mice developed cholesterol gallstones with an incidence of 70% by 5 weeks and 80% by 10 weeks after feeding of the cholesterol diet. Diabetic mice fed the ordinary diet also developed stones (23%) by 10 weeks. In the diabetic mice, the gallbladder was enlarged about threefold, and biliary lipid concentration, diet intake, and fecal excretion of sterols and bile acids increased but body weight decreased. Cholic acid and beta-muricholic acid comprised over 40% each of the total biliary bile acids in normal mice, but cholic acid increased to about 80% and beta-muricholic acid decreased to a few percent in the diabetic mice. Fecal excretion of bile acids increased after cholesterol feeding in both normal and diabetic mice, but the increased bile acid in the normal animals was beta-muricholic acid and that in the diabetic mice was deoxycholic acid. The mice that developed gallstones showed a marked increase in biliary cholesterol value and decreases in gallbladder bile and bile acid concentration, but no difference in biliary and fecal bile acid composition, bile acid synthesis, fecal sterols, or plasma and liver lipid levels. Cholesterol absorption was increased in the diabetic mice when examined by plasma 14C/3H ratio and fecal 14C-labeled sterol excretion after a single oral administration of [14C]cholesterol and a simultaneous intravenous injection of [3H]cholesterol. These data led to the conclusion that cholesterol gallstones developed in alloxan-diabetic mice fed excess cholesterol, due to the hyperphagia and the enhancement of cholesterol absorption caused by increases in the synthesis and secretion of cholic acid.     

Effect of dietary tomatine on cholesterol metabolism in the rat

Tomatine is a virtually nonabsorbable saponin which has been used as an antifungal agent and analytically as a cholesterol precipitant. It was used in this study to determine whether or not it can form a complex with cholesterol in vivo in the rat intestine and what effects such complex formation would have on cholesterol metabolism. Rats that were fed tomatine as 1% of the diet had a decreased uptake of dietary cholesterol by the liver, an increased rate of hepatic and intestinal cholesterol synthesis as well as a partial offsetting of the dietary cholesterol-induced decrease in hepatic cholesterogenesis, and an apparent increase in sterol excretion without an effect on bile acid excretion. In vitro, tomatine did not sequester cholic acid as did cholestyramine. The results show that tomatine has an effect on cholesterol absorption and on other aspects of lipid metabolism in the rat similar to that of cholestyramine, with the notable exception that tomatine increased sterol excretion while cholestyramine increased bile acid excretion. It was suggested that tomatine forms a nonabsorbable complex with cholesterol in the rat intestine.     

Evaluation of an isotope ratio method for measurement of cholesterol absorption in man

Recently an isotope ratio method (IRM) was developed for measuring cholesterol absorption in rats by analysis of radioactivity in peripheral blood (Zilversmit, D. B. 1972. Proc. Soc. Exp. Biol. Med. 140: 862-865). To validate it in man we have compared cholesterol absorption by a fecal radioactivity method (FRM) with that simultaneously measured by IRM in 14 patients (15 experiments) hospitalized on a metabolic ward. Cholesterol absorption by FRM was assayed as fecal recovery of orally administered [(14)C]cholesterol, after correction with markers for fecal flow (chromic oxide) and cholesterol degradation (beta-sitosterol). Simultaneously, [(3)H]cholesterol was administered intravenously, and the dose-normalized ratio of [(14)C]- to [(3)H]cholesterol was repeatedly assayed in plasma. After 72 hours the ratio became constant in each patient and remained so for as long as 63 weeks (five additional outpatient studies). In three patients the fecal data were unsatisfactory because of poor recoveries of chromic oxide and radioactive cholesterol. In the remaining 11 patients (12 experiments) the mean cholesterol absorption by IRM was 42.1% (range 15.7-62.9%) and by FRM 36.6% (range 13.8-58.8%). There was good to excellent agreement between the two methods in the same patient, except in one experiment. Statistical analysis of these 12 comparisons by estimating confidence intervals showed that we can be 95% confident that the two absorption methods will produce results within 5 percentage points, and 99% confident that the differences are less than 7 percentage points. Although we conclude that IRM affords results that are concordant with those obtainable by earlier validated methods, we urge that its suitability for outpatient studies be further examined in more extensive trials.     

Use of 3H-labeled triether, a nonabsorbable oil-phase marker, to estimate fat absorption in rats with cholestyramine-induced steatorrhea

A tritium-labeled glycerol triether was tested as a nonabsorbable oil-phase marker in studies of fat absorption in normal rats and in rats with steatorrhea induced by various doses of cholestyramine. Animals were fed a test meal containing (3)H-labeled triether and (14)C-labeled trilinolein. Fat absorption was estimated in the following three ways: (a) by isotope ratios (the change in (3)H/(14)C in the test meal and in feces); (b) by isotope recovery (the total fecal excretion of (14)C radioactivity); and (c) by chemical recovery (the total fecal fat excretion). Absorption calculated from isotope ratios agreed well with that calculated from isotope recovery over a range of fat absorption of 50-100%, thus validating the use of this lipid marker under these conditions of fat malabsorption. Absorption calculated from chemical recovery was consistently poorer than that calculated from isotope ratios or isotope recovery, thus suggesting that cholestyramine increased the excretion of nondietary (endogenous) fat. Triether may be of value for studying the absorption of compounds present predominantly in the oil phase during digestion and may have significant advantages over other proposed lipid markers.     

Evaluation of the contribution of dietary cholesterol to hypercholesterolemia in diabetic rats and of sitosterol as a recovery standard for cholesterol absorption

The contribution of dietary cholesterol to hypercholesterolemia in diabetic rats fed chow ad libitum was evaluated. Diabetes was induced with streptozotocin, and the intake, absorption, and subsequent tissue distribution of dietary cholesterol were measured. Absorption was measured as the difference between [3H]cholesterol intake and fecal 3H-labeled neutral sterol excretion, using both [14C]sitosterol (added to diet) and [14C]cholesterol (added to feces) as recovery markers. [3H]Cholesterol absorption was underestimated by 1-3% using [14C]sitosterol as a recovery standard, due to the 7-8% absorption of sitosterol. After 3 weeks of diabetes, rats were hyperphagic, thereby increasing dietary cholesterol intake 2-fold. [3H]Cholesterol absorption was significantly increased from 69% in controls to 78% in diabetics, whereas [14C]sitosterol absorption was unaffected. With increased dietary cholesterol intake and decreased whole body cholesterol synthesis (Diabetes. 1983. 32: 811-819), influx from diet equaled for exceeded influx from synthesis. The amounts of 3H-labeled neutral sterol recovered from the small intestine, periphery, and plasma were increased 3- to 4-fold in the diabetic rats. Furthermore, the degree of hypercholesterolemia in diabetic rats was directly related to the fraction of plasma cholesterol derived from the diet. We conclude that the 2.3-fold increase in absorbed dietary cholesterol resulting from hyperphagia and, to a lesser extent, from increased fractional absorption, contributes to the hypercholesterolemia of diabetic rats fed chow ad libitum.     

Lymphatic absorption of fatty acids and cholesterol in the neonatal rat

High-fat diets are essential in suckling animals to ensure adequate calories for postnatal growth, but their lymphatic transport of dietary lipids has not been characterized. We established a lymph fistula model in suckling rats to quantify intestinal uptake and lymphatic transport of dietary lipids and analyzed lipoprotein fractions. Suckling 19-day-old Sprague-Dawley rats had their mesenteric lymph ducts cannulated and gastroduodenal tubes inserted. After overnight recovery, [(3)H]triolein and [(14)C]cholesterol were infused for 6 h. Of the total dose, only 38% of triolein and 24% of cholesterol were transported in the lymph of suckling rats. Analyses of residual luminal contents and intestinal mucosal homogenate showed neither reduced absorption nor delayed mucosal processing of ingested lipids to be the cause. Thin-layer chromatographic analysis of radioactive mucosal lipids, however, showed a predominance of free fatty acids (60%) and free cholesterol (67%), implying impaired esterification capacity in these animals. We speculate that this reduced esterification allows for portal transport or direct enterocyte metabolism of dietary lipids.     

Roles of nuclear receptors in the up-regulation of hepatic cholesterol 7alpha-hydroxylase by cholestyramine in rats

Nuclear receptors are involved in regulating the expression of cholesterol 7alpha-hydroxylase (CYP7A1), however, their roles in the up-regulation of CYP7A1 by cholestyramine (CSR) are still unclear. In the present study, male Wistar rats were divided into four groups and fed [high sucrose + 10% lard diet] (H), [H + 3% CSR diet] (H + CSR), [H + 0.5% cholesterol + 0.25% sodium cholate diet] (C), or [C + 3% CSR diet] (C + CSR) for 2 weeks. Cholestyramine decreased serum and liver cholesterol levels significantly in rats fed C-based diets, but had no effect on these parameters in rats fed H-based diets. Cholestyramine raised hepatic levels of CYP7A1 mRNA and activity in both groups. The gene expression of hepatic ATP-binding cassettes A1 and G5, regulated by liver X receptor (LXR), were unchanged and down-regulated by cholestyramine, respectively. The mRNA levels of the hepatic ATP-binding cassette B11 and short heterodimer partner (SHP), regulated by farnesoid X receptor (FXR), were not changed by cholestyramine. C-based diets, which contained cholesterol and cholic acid, increased SHP mRNA levels compared to H-based diets. Consequently, in rats fed the C+CSR diet, hepatic FXR was activated by dietary bile acids, but the hepatic CYP7A1 mRNA level was increased 16-fold compared to that in rats fed an H diet. These results suggest that cholestyramine up-regulates the expression of CYP7A1 independently via LXR- or FXR-mediated pathways in rats.     

Delineation of biochemical, molecular, and physiological changes accompanying bile acid pool size restoration in Cyp7a1(-/-) mice fed low levels of cholic acid

Cholesterol 7α-hydroxylase (CYP7A1) is the initiating and rate-limiting enzyme in the neutral pathway that converts cholesterol to primary bile acids (BA). CYP7A1-deficient (Cyp7a1(-/-)) mice have a depleted BA pool, diminished intestinal cholesterol absorption, accelerated fecal sterol loss, and increased intestinal cholesterol synthesis. To determine the molecular and physiological effects of restoring the BA pool in this model, adult female Cyp7a1(-/-) mice and matching Cyp7a1(+/+) controls were fed diets containing cholic acid (CA) at modest levels [0.015, 0.030, and 0.060% (wt/wt)] for 15-18 days. A level of just 0.03% provided a CA intake of ~12 μmol (4.8 mg) per day per 100 g body wt and was sufficient in the Cyp7a1(-/-) mice to normalize BA pool size, fecal BA excretion, fractional cholesterol absorption, and fecal sterol excretion but caused a significant rise in the cholesterol concentration in the small intestine and liver, as well as a marked inhibition of cholesterol synthesis in these organs. In parallel with these metabolic changes, there were marked shifts in intestinal and hepatic expression levels for many target genes of the BA sensor farnesoid X receptor, as well as genes involved in cholesterol transport, especially ATP-binding cassette (ABC) transporter A1 (ABCA1) and ABCG8. In Cyp7a1(+/+) mice, this level of CA supplementation did not significantly disrupt BA or cholesterol metabolism, except for an increase in fecal BA excretion and marginal changes in mRNA expression for some BA synthetic enzymes. These findings underscore the importance of using moderate dietary BA levels in studies with animal models.     

Quantification of cholesterol absorption in man by fecal analysis after the feeding of a single isotope-labeled meal

The fecal excretion of cholesterol-4-(14)C and -sitosterol-22,23-(3)H has been studied in normal human subjects after they had ingested a single meal containing the radioactive substances. When 150 mg of -sitosterol, dispersed in the butter of a standard breakfast, was fed to 20 subjects the mean recovery of isotope in the feces was 90%. When plant sterols (70% -sitosterol, 30% campesterol) were fed together with cholesterol and used as an internal standard to correct for losses of cholesterol during intestinal transit and analytical procedures, excretion of dietary cholesterol was found to be 60-80%, irrespective of the amount fed over the range 150-1910 mg. If absorption of cholesterol is calculated from these figures, no saturation of the cholesterol absorption mechanism is indicated for the amounts of cholesterol fed in this investigation. The reason for the differences between these findings and those previously reported by other procedures is not clear, but may be related to the acute administration of a single dose of cholesterol in this study.     

Alteration of biliary ursodeoxycholic acid in guinea pig during early stages of cholestyramine feeding

The effects of cholestyramine feeding on biliary ursodeoxycholic acid, fecal excretion of bile acids and neutral sterols on cholesterol 7α-hydroxylase and hepatic HMG-CoA reductase were examined in the guinea pig. In the bile there was a 57% decrease in the concentration of ursodeoxycholic acid while an increase was observed in the concentration of chenodeoxycholic acid. Cholestyramine feeding for ten days resulted in a decrease in plasma cholesterol levels and an increase in both hepatic HMG-CoA reductase and cholesterol 7α-hydroxylase activities. The fecal excretion of both bile acids and neutral sterols was significantly increased.     

Changes in Plasma Lipid Levels in Young Healthy Volunteers by Adding an Extruder-cooked Soy Protein to Conventional Meals

The serum cholesterol level in rats was significantly decreased in a group fed on a soyprotein peptic hydrolyzate (SPH) when compared with a group fed on a casein tryptic hydrolyzate (CTH). The fecal excretion of total steroids was significantly greater with rats fed on the SPH diet when compared with the CTH diet. The results of CaCo-2 studies clearly suggest that the suppression of cholesterol absorption in the intestinal epithelia is part of the mechanism for the hypocholesterolemic action induced by SPH.