Fecal Excretion Of Neutral Steroids Research Articles

MicroRNA-206 as a potential cholesterol-lowering drug is superior to statins in mice

Hypercholesterolemia is frequently intertwined with hepatosteatosis, hypertriglyceridemia, and hyperglycemia. This study is designed to assess the therapeutic efficacy of miR-206 in contrast to statins in the context of managing hypercholesterolemia in mice. We previously showed that miR-206 is a potent inhibitor of de novo lipogenesis (DNL), cholesterol synthesis, and gluconeogenesis in mice. Given that these processes occur within hepatocytes, we employed a mini-circle (MC) system to deliver miR-206 specifically to hepatocytes (designated as MC-miR-206). A single intravenous injection of MC-miR-206 maintained high levels of miR-206 in the liver for at least two weeks, thereby maintaining suppression of hepatic DNL, cholesterol synthesis, and gluconeogenesis. MC-miR-206 significantly reduced DNA damage, endoplasmic reticulum and oxidative stress, and hepatic toxicity. Therapeutically, both MC-miR-206 and statins significantly reduced total serum cholesterol and triglycerides as well as LDL cholesterol and VLDL cholesterol in mice maintained on the normal chow and high-fat high-cholesterol diet. MC-miR-206 reduced liver weight, hepatic triglycerides and cholesterol, and blood glucose, while statins slightly increased hepatic cholesterol and blood glucose and failed to affect levels of liver weight and hepatic triglycerides. Mechanistically, miR-206 alleviated hypercholesterolemia by inhibiting hepatic cholesterol synthesis, while statins increased HMGCR activity, hepatic cholesterol synthesis, and fecal-neutral steroid excretion. MiR-206 facilitates the regression of hypercholesterolemia, hypertriglyceridemia, hyperglycemia, and hepatosteatosis. MiR-206 outperforms statins by reducing hyperglycemia, hepatic cholesterol levels, and hepatic toxicity.

Medium-Chain Fatty Acids Enhanced the Excretion of Fecal Cholesterol and Cholic Acid in C57BL/6J Mice Fed a Cholesterol-Rich Diet

The objective of the present study was to investigate the cholesterol-reducing effect of medium-chain fatty acids (MCFAs) completed by elevated excretion of fecal neutral steroids and/or bile acids. Blood and liver lipid profiles, fecal neutral steroids, bile acids, and mRNA and protein expression of the genes relevant to cholesterol homeostasis were measured and analyzed in C57BL/6J mice fed a cholesterol-rich diet with 2% caprylic acid or capric acid for 12 weeks. Blood total cholesterol and low-density lipoprotein cholesterol (LDL-c) levels were reduced significantly as compared to diet with palmitic acid or stearic acid. Caprylic acid promoted the excretion of fecal neutral steroids, especially cholesterol. The excretion of fecal bile acids, mainly in the form of cholic acid was enhanced and accompanied by elevated expression of mRNA and the protein of hepatic cholesterol 7α-hydroxylase (CYP7A1). These results indicate that MCFAs can reduce blood cholesterol by promoting the excretion of fecal cholesterol and cholic acid.

Effect of Cheonggukjang made with germinated soybean on lipid contents and fecal excretion of neutral steroids in rats fed a high cholesterol diet

This study was conducted to investigate the effect of cheonggukjang made with soybean germinated under dark and light conditions on lipid content and fecal neutral steroids in rats fed with a high cholesterol diet. Rats were divided into 4 groups: high cholesterol diet (HC); high cholesterol diet containing normal cheonggukjang (HNC); high cholesterol diet containing cheonggukjang made with soybean germinated under dark condition (HDC); high cholesterol diet containing cheonggukjang made with soybean germinated under light condition (HLC). Dietary supplementation with light-reacted cheonggukjang decreased hepatic triglycerides, compared with the other groups. Fecal excretion of total lipids and triglycerides increased when fed with cheonggukjang made with soybean germinated under light condition. Fecal excretion of coprostanol, cholesterol, and coprostanone tended to increase in the cheonggukjang-supplemented groups. These results suggest that dietary supplementation with cheonggukjang made with germinated soybean might prevent hyperlipidemia by improving the lipid metabolism through decreasing the liver triglycerides contents and increasing fecal excretion of triglycerides.

Mechanisms Underlying Decreased Hepatic Triacylglycerol and Cholesterol by Dietary Bitter Melon Extract in the Rat

In these studies, we focused on finding the mechanism(s) underlying the bitter melon (Momordica charantia L.) methanol fraction (MF)-dependent reduction in the concentration of hepatic triacylglycerol (TAG) and cholesterol in the rat. Rats were fed diets containing low (5 %) fat for 2 weeks (experiment 1), or low (5 %) and high (15 %) fat for a longer period of 8 weeks (experiment 2). MF was supplemented at 1 % level in both experiments. After feeding, rats were sacrificed, and their livers were prepared as slices and hepatocytes, followed by incubation with [1(2)-¹⁴C] acetate or [1-¹⁴C] oleic acid (18:1 n-6). Under these conditions, we found that rats fed diets containing MF, as compared to those without MF, showed: (1) no adverse effects on food intake and growth, (2) a decreased hepatic TAG and total cholesterol, irrespective of the difference in dietary fat level or feeding period, and (3) a decreased incorporation of [1(2)-(¹⁴C] acetate and [1-¹⁴C] oleic acid into TAG of liver slices and hepatocytes. MF-supplemented rats also showed no altered incorporation of labeled acetate into cholesterol and cholesterol ester, an increased fecal excretion of neutral steroids, but not of acidic steroids, and an enhanced mRNA abundance of carnitine palmitoylacyltransferase I, which is the rate-limiting enzyme for fatty acid oxidation. These results suggest that dietary MF decreases hepatic TAG synthesis while enhancing fatty acid oxidation, thereby reducing the concentration of hepatic TAG. The liver cholesterol-lowering effect of MF, however, is probably mediated through an increased fecal excretion of neutral steroids, without an effect on cholesterogenesis.

Rice α-globulin decreases serum cholesterol concentrations in rats fed a hypercholesterolemic diet and ameliorates atherosclerotic lesions in apolipoprotein E-deficient mice

The hypocholesterolemic and antiatherogenic effects of rice α-globulin remain unclear. We investigated the hypocholesterolemic effect of rice α-globulin in rats fed a hypercholesterolemic diet. The rats were divided into 4 groups and were orally administrated the following three proteins or a vehicle for 4weeks: rice protein, rice α-globulin, or soy β-conglycinin at a dose of 100mg/kg body weight or carboxymethylcellulose to the control rats. In the rice α-globulin group, serum cholesterol concentrations were 28% lower than the control group and fecal neutral steroid excretion was increased by 30%. The hypocholesterolemic effect of rice α-globulin was equal to soy β-conglycinin in SD rats fed the hypercholesterolemic diet. However, the serum cholesterol concentrations in the rice protein group did not change compared to the control group. To investigate the antiatherogenic effects of rice α-globulin, male apolipoprotein E-deficient mice were orally administered the same dose of rice α-globulin for 9weeks. The en face lesion area in the aorta was 46% lower than in the control group. In conclusion, administration of rice α-globulin improves hypercholesterolemia in rats fed a hypercholesterolemic diet by increasing the fecal excretion of neutral sterols, and inhibits atherosclerosis development in apolipoprotein E-deficient mice. The anti-atherosclerotic effect exerts by mechanism(s) other than the regulation of serum MCP-1 and NO concentrations.

Modified Soybean Affects Cholesterol Metabolism in Rats Similarly to a Commercial Cultivar

The consumption of soy protein lowers blood cholesterol in humans and animals. Breeding may alter the physiological effects of soybeans, such as its cholesterol-lowering property. Our hypothesis is that breeding affects the hypocholesterolemic effect of soy by modulating the expression of key hepatic enzymes related to cholesterol and bile acid biosynthesis, as well as altering fecal neutral and acidic steroid excretion. Therefore the aim of this study was to evaluate the effect of a new Brazilian soybean cultivar (UFV-116), lacking lipoxygenases 2 and 3, compared with a commercial cultivar (OCEPAR-19), on 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) and cholesterol 7α-hydroxylase (CYP7A) mRNA expression and fecal steroid output in rats. Thirty-six male rats were fed UFV-116, OCEPAR-19, or casein as the protein source, with or without addition of dietary cholesterol (0.25%). Blood and liver cholesterol, HMGR and CYP7A mRNA abundance, and fecal excretion of steroids were measured. Blood and liver cholesterol levels were lowered by both soybean cultivars, with and without cholesterol, but UFV-116 was more effective when included in the cholesterol-free diet. Both soy diets promoted lower levels of HMGR mRNA, higher levels of CYP7A mRNA, and higher excretion of fecal secondary bile acids. There was higher fecal neutral steroid output when cholesterol was added to all diets. These data show that both soybean cultivars acted similarly in lowering serum and hepatic cholesterol; therefore, breeding did not affect the hypocholesterolemic effect of the new cultivar.

Comparison of Effects of Dietary Unesterified and Esterified Plant Sterols on Cholesterol Absorption in Rats

Effects of dietary unesterified plant sterols and plant sterol oleates and stearates on absorption and metabolism of cholesterol were compared in rats fed a cholesterol-supplemented diet. Fecal excretion of neutral steroids (cholesterol plus coprostanol) in rats fed unesterified plant sterols or plant sterol oleates was significantly higher than in those fed the control diet or plant sterol stearates. Deposition of cholesterol in the liver was significantly lower in rats fed unesterified plant sterols or plant sterol oleates than in those fed the control diet or plant sterol stearates. No significant difference was observed in fecal excretion of cholesterol plus coprostanol and hepatic cholesterol concentration between unesterified plant sterols and plant sterol oleates. Unesterified plant sterols were significantly more effective to reduce lymphatic recovery of radiolabeled cholesterol given to the stomach than plant sterol oleates. Although our observations suggest a possibility that unesterified plant sterols are potentially more effective to inhibit cholesterol absorption than plant sterol oleates in rats, difference in the activity is substantially small between these two forms of plant sterols.

Soybean Protein Hydrolysate Improves Plasma and Liver Lipid Profiles in Rats Fed High-Cholesterol Diet

Objective: This investigation attempted to clarify the hypolipidemic effects of non-dialyzed soybean protein hydrolysate (NSPH), which is hydrolyzed by pepsin from soybean acid-precipitated protein (APP), in rats fed a cholesterol-rich diet.Methods: Forty Sprague-Dawley rats were divided into four groups as the control group (19.7% casein), the APP group (14.7% casein + 5% APP), the NSPH group (14.7% casein + 5% NSPH), and the ISO group (19.7% casein + 0.0013% soy isoflavone).Results: After 12-week experimental period, the APP and NSPH groups had a significant lower plasma total cholesterol, triglycerides, and LDL-cholesterol concentrations compared with the control group. Additionally, the atherosclerosis index in APP and NSPH group had also markedly decreased. Liver cholesterol and triglyceride contents of the APP and NSPH group were significantly lower than those of the control group. There were no different in plasma LDL-C, liver cholesterol and triglycerides between the ISO group and control group. Fecal excretion of neutral steroids and nitrogen compounds was significantly higher in the APP and NSPH groups than that in the control group. An in vitro study also showed that NSPH, compared with casein, obviously decreased cholesterol micellar solubility.Conclusion: These results suggested that NSPH may decrease lipid accumulation in the liver and have a hypolipidemic effect by enhancing excretion and inhibiting absorption of lipids.

Studies on the Cholesterol-Free Mouse

Characterization of cholesterol homeostasis in male mice with a genetic inactivation of 3beta-hydroxysteroid-delta24-reductase, causing replacement of almost all cholesterol with desmosterol. There was an increase in hepatic sterol synthesis and markedly increased fecal loss of neutral sterols. Fecal excretion of bile acids was similar in knockout mice and in controls. The composition of bile acids was changed, with reduced formation of cholic acid. It was shown that both Cyp7a1 and Cyp27a1 are active toward desmosterol, consistent with the formation of normal bile acids from this steroid. The levels of plant sterols were markedly reduced. Hepatic mRNA levels of 3-hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) reductase, Srebp-1c, Srebp-2, Cyp7a1, Abcg5, Abcg8, and Fas were all significantly increased. The changes in hepatic mRNA levels in combination with increased biliary and fecal excretion of neutral steroids, reduced tissue levels of plant sterols, increased plasma levels of triglyceride-rich VLDL, are consistent with a strong activation of LXR-targeted genes. The markedly increased fecal loss of neutral sterols may explain the fact that the Dhcr24-/- mice do not accumulate dietary cholesterol. The study illustrates the importance of the integrity of the cholesterol structure--presence of a double bond in the steroid side-chain is compatible with life but is associated with serious disturbances in sterol homeostasis.

Campest-5-en-3-one, an oxidized derivative of campesterol, activates PPARα, promotes energy consumption and reduces visceral fat deposition in rats

Dietary campest-5-en-3-one (campestenone), an oxidized derivative of campesterol, significantly reduced visceral fat weight and the concentration of triacylglycerol in serum and liver of rats. Dietary campestenone dramatically increased the activities and the mRNA expressions of mitochondrial and peroxisomal enzymes involved in β-oxidation in the liver. Campestenone activated human peroxisome proliferator-activated receptor (PPAR) α as determined using the novel GAL4 ligand-binding domain chimera assay system with coactivator coexpression. In contrast, dietary campestenone reduced the activities and the mRNA expressions of enzymes involved in fatty acid synthesis, except for the malic enzyme. Dietary campestenone decreased the sterol regulatory element binding protein-1 (SREBP-1) mRNA level. Energy expenditure was significantly higher in the feeding of campestenone in rats. Dietary campestenone reduced hepatic cholesterol concentration and increased fecal excretion of neutral steroids originated from cholesterol. Lymphatic absorption of cholesterol was reduced by the coadministration of campestenone in rats cannulated in the thoracic duct. These observations suggest a possibility that campestenone has an ability to prevent coronary heart disease by improving obesity and abnormality of lipid metabolism.

Dose‐dependent hypocholesterolemic actions of dietary apple polyphenol in rats fed cholesterol

The dose-dependent hypocholesterolemic and antiatherogenic effects of dietary apple polyphenol (AP) from unripe apple, which contains approximately 85% catechin oligomers (procyanidins), were examined in male Sprague-Dawley rats (4 wk of age) given a purified diet containing 0.5% cholesterol. Dietary AP at 0.5 and 1.0% levels significantly decreased the liver cholesterol level compared with that in the control (AP-free diet-fed) group. Dietary AP also significantly lowered the serum cholesterol level compared with that in the control group. However, the HDL cholesterol level was significantly higher in the 1.0% AP-fed group than in the control group. Accordingly, the ratio of HDL-cholesterol/total cholesterol was significantly higher in the 0.5% AP-fed group and 1.0% AP-fed group than in the control group. Moreover, the atherogenic indices in the 0.5 and 1.0% AP-fed groups were significantly lower than those in the control group. The activity of hepatic cholesterol 7alpha-hydroxylase tended to be increased by dietary AP in a dose-dependent manner. In accord with this observation, dietary AP increased the excretion of acidic steroids in feces. Dietary AP also significantly promoted the fecal excretion of neutral steroids in a dose-dependent manner. These observations suggest that dietary AP at a 0.5 or 1.0% level exerts hypocholesterolemic and antiatherogenic effects through the promotion of cholesterol catabolism and inhibition of intestinal absorption of cholesterol.

Resistant starches of beans reduce the serum cholesterol concentration in rats.

We examined the effects of the resistant starches of adzuki (Vigna angularis), kintoki (Phaseolus vulgaris, variety), and tebou (P. vulgaris, variety) beans on the lipid metabolism in rats. Rats were fed a cholesterol-free diet with 25 g of cornstarch (CS)/100 g diet, 25 g of adzuki starch (AS)/100 g diet, 25 g of kintoki starch (KS)/100 g diet, or 25 g of tebou starch (TS)/100 g diet for 4 wk. The cecal contents in the TS group were significantly higher than those in the CS and KS groups. There were no significant differences in body weight or food intake among the groups. The relative liver weight in the CS group was significantly greater than that of the AS, KS, and TS groups. The serum total cholesterol, VLDL+IDL+LDL-cholesterol, and triglyceride concentrations in the AS, KS, and TS groups were significantly lower than those in the CS group throughout the feeding period. Though the total hepatic cholesterol concentration in the TS group was significantly higher than that in the KS group, there were no significant differences between the CS and other starch groups. The cecal pH value in the CS group was significantly higher than that of the bean starch groups. The cecal butyric acid concentrations in the AS, KS, and TS groups were significantly higher than that in the CS group, and the cecal total short-chain fatty acid (SCFA) concentrations in the AS and TS groups were significantly higher than those of the CS group. The fecal cholesterol excretion of the AS, KS, and TS groups were significantly higher than that in the CS group. The fecal coprostanol excretion in the AS group was significantly higher than that in the CS group. There was a negative correlation between the serum VLDL+IDL+LDL-cholesterol concentration and fecal neutral steroid excretion (r = -0.664, p < 0.001) in the present experiment. Furthermore, the cecal total SCFA concentration was negatively correlated with the serum VLDL+IDL+LDL-cholesterol concentration (r = -0.665, p < 0.001) and positively correlated with fecal neutral steroid excretion (r = 0.481, p < 0.05). The cecal butyric acid level was also negatively correlated with the serum VLDL+IDL+LDL-cholesterol concentration (r = -0.609, p < 0.01) and positively correlated with fecal neutral steroid excretion (r = 0.658, p < 0.001). The results suggest that AS, KS, and TS elevate cecal SCFA concentration, in particular butyric acid concentration, and fecal neutral sterol excretion, and lower the serum total cholesterol level.

Raising intestinal contents viscosity leads to greater excretion of neutral steroids but not bile acids in hamsters and rats

To examine the effect of intestinal contents viscosity on fecal steroid excretion independent of colonic fermentation, hamsters and rats were fed cholesterol-containing diets containing either cellulose or different viscosity grades of hydroxypropyl methylcellulose (HPMC), a non-fermentable fiber, as the dietary fiber source. HPMC feeding relative to cellulose significantly lowered plasma cholesterol in hamsters and liver cholesterol in rats. Fecal neutral steroid excretion was significantly greater in both species consuming HPMC compared to cellulose. Fecal bile acid excretion was not altered in hamsters, but was reduced in rats fed HPMC compared to cellulose. Thus, greater intestinal contents supernatant viscosity results in reduced plasma (hamster) or liver (rat) cholesterol and greater neutral steroid excretion, whereas bile acid excretion is unaffected or reduced. This suggests that viscosity is the principal characteristic of dietary fiber responsible for cholesterol lowering, and that this effect is due to increased excretion of cholesterol from the body.

Plant sterols alter bile acid metabolism and reduce cholesterol absorption in hamsters fed a beef-based diet

This study examined the cholesterol-lowering properties of dietary plants sterols (PS) when consumed in a beef-based diet. Male Syrian hamsters were fed freeze-dried ground beef supplemented with maltodextrin, vegetable oil, vitamins, minerals, and soybean sterol esters at 0.0, 0.3, 1.0, or 3.0% sterol by weight of the diet. After 4 weeks, plasma and liver total cholesterol concentrations were significantly and incrementally reduced at all levels of dietary PS tested compared to no dietary PS. Cholesterol absorption was also significantly reduced by dietary PS, resulting in greater fecal excretion of neutral steroids. Total bile acid excretion was also significantly increased with PS feeding. A novel finding in the present study was that PS feeding caused an alteration in the gallbladder bile acid profile, resulting in a significantly lower hydrophobicity index. The present study demonstrates that the consumption of ground beef containing PS can significantly lower plasma cholesterol concentration at relatively low doses, indicating that ground beef can be used as a functional food to lower cholesterol while providing superior nutritional benefits over the high fat PS-containing margarines and salad dressings currently available.

Effects of Brewer's Yeast Cell Wall on Fecal Steroid Excretion in Rats.

To reveal the mechanism(s) of the cholesterol-lowering effect of brewer’s yeast cell wall (BYC), we examined the effect of BYC on fecal steroid excretion in rats fed a high-cholesterol and -fat (HCF) diet or a cholesterol-free standard (STD) diet. Male Sprague-Dawley rats were fed an HCF diet or an HCF diet supplemented with 5% or 10% BYC for 14 days. The addition of BYC to the HCF diet dose-dependently reduced the increment of serum total cholesterol concentration and increased the fecal bile acid and neutral steroid(cholesterol and coprostanol) excretion levels. In this experiment, a negative correlation between serum total cholesterol concentration and fecal bile acid excretion level was observed; however, a correlation between serum total cholesterol concentration and fecal neutral steroid excretion level was not observed. Next, male Sprague-Dawley rats were fed an STD diet or an STD diet supplemented with 5% or 10% BYC for 14 days, to investigate whether BYC could lower serum total cholesterol concentration in the rats with normal serum cholesterol concentrations. The addition of BYC to the STD diet also slightly increased the fecal bile acid excretion level; however, it did not affect the serum cholesterol concentration. Furthermore, we examined whether BYC can reduce the serum total cholesterol concentration in Sprague-Dawley rats fed an HCF diet prior to the administration of BYC, to increase the serum total cholesterol concentration. In this experimental model, BYC reduced serum total cholesterol concentration and increased fecal total steroid excretion level, and a negative correlation between serum total cholesterol concentration and fecal bile acid excretion level was observed. These results suggest that BYC reduces serum total cholesterol concentration by increasing fecal bile acid excretion level.

Effects of diets enriched in n-6 or n-3 fatty acids on cholesterol metabolism in older rats chronically fed a cholesterol-enriched diet.

Hypocholesterolemic effects in older animals after long-term feeding are unknown. Therefore, aged rats (24 wk of age) fed a conventional diet were shifted to diets containing 10% perilla oil [PEO; oleic acid + linoleic acid + alpha-linolenic acid; n-6/n-3, 0.3; polyunsaturated fatty acid/saturated fatty acid (P/S), 9.6], borage oil [oleic acid + linoleic acid + alpha-linolenic acid; n-6/n-3, 15.1; P/S, 5.3], evening primrose oil (EPO; linoleic acid + gamma-linolenic acid; P/S, 10.5), mixed oil (MIO; oleic acid + linoleic acid + gamma-linolenic acid + alpha-linolenic acid; n-6/n-3, 1.7; P/S, 6.7), or palm oil (PLO; palmitic acid + oleic acid + linoleic acid; n-6/n-3, 25.3; P/S, 0.2) with 0.5% cholesterol for 15 wk in this experiment. There were no significant differences in the food intake and body weight gain among the groups. The liver weight in the PEO (n-6/n-3, 0.3) group was significantly higher than those of other groups in aged rats. The serum total cholesterol and very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) + low density lipoprotein (LDL)-cholesterol concentrations of the PLO (25.3) group were consistently higher than those in the other groups. The serum high density lipoprotein cholesterol concentrations of the PEO (0.3) and EPO groups were significantly lower than in the other groups at the end of the 15-wk feeding period. The liver cholesterol concentration of the PLO (25.3) group was significantly higher than those of other groups. There were no significant differences in the hepatic LDL receptor mRNA level among the groups. Hepatic apolipoprotein (apo) B mRNA levels were not affected by the experimental conditions. The fecal neutral steroid excretion of the PLO (25.3) group tended to be low compared to the other groups. The results of this study demonstrate that both n-6 fatty acid and n-3 fatty acids such as gamma-linolenic acid and alpha-linolenic acid inhibit the increase of serum total cholesterol and VLDL + IDL + LDL-cholesterol concentrations of aged rats in the presence of excess cholesterol in the diet compared with dietary saturated fatty acid.

Hypocholesterolemic effect of indigestible fraction of Chlorella regularis in cholesterol-fed rats.

The effects of Chlorella regularis powder (CP) and Chlorella regularis indigestible fraction (CIF) on serum and liver lipid concentrations and on fecal steroid excretion were estimated in rats fed diets containing 5 g/kg cholesterol and 2.5 g/kg sodium cholate. The ingestion of 12.7% CP or 5.3% CIF did not influence food intake or growth. CP and CIF decreased the levels of serum cholesterol, but had no effect on the levels of serum triacylglycerol and phospholipid. Liver cholesterol contents were lower in the CP and CIF groups than in the control group, but CP and CIF did not affect liver triacylglycerol content. CP and CIF increased the total amount of fecal neutral steroids excreted, but did not modify the total bile acid excretion. However, the soluble bile acid concentrations of reconstituted fecal water in the rats fed CP and CIF diets were lower than the control value. Moreover, CP and CIF had a high bile acid binding capacity in vitro. These results indicated that CIF had a hypocholesterolemic effect and enhanced fecal neutral steroid excretion while decreasing the soluble fecal bile acid concentration.

Effects of the Oral Administration of Green Tea Polyphenol and Tannic Acid on Serum and Hepatic Lipid Contents and Fecal Steroid Excretion in Rats.

Green tea polyphenol (Polyphenon) or tannic acid was administered orally to rats at a dose of 0.01-1.0 or 0.1-1.0 g/kg for 23 days, and changes both in serum and hepatic lipid concentrations and in fecal steroid excretion were examined. The administration of 0.2-1.0 g/kg of Polyphenon caused a significant decrease in levels of serum HDL-cholesterol, whereas tannic acid had no significant effect on serum lipid concentrations. The hepatic triglyceride concentration was significantly higher than controls in rats given more than 0.5 g/kg of Polyphenon, whereas both hepatic triglyceride and phospholipid concentrations were significantly higher after tannic acid administration. Serum thiobarbituric acid reactive substances were significantly low in rats given either 1.0 g/kg of Polyphenon or more than 0.1 g/kg of tannic acid. Fecal neutral steroid excretion increased significantly in rats given a dose of 1.0 g/kg of either Polyphenon or tannic acid. The excretion of fecal bile acids increased significantly in rats given 0.2 g/kg of tannic acid, but then tended to decrease at higher doses; however, excretion of fecal bile acids did not change after Polyphenon administration. We found that alterations in the compositions of fecal neutral steroids and bile acids were independent of the tannic acid or Polyphenon dose: the ratio of coprostanol to cholesterol decreased significantly in rats given 0.05-0.2 g/kg of Polyphenon or 0.5 g/kg of tannic acid; and the ratio of cholic-acid-derived bile acids to chenodeoxycholic-acid-derived bile acids decreased significantly after administration of 0.05, 0.2 and 0.5 g/kg of Polyphenon or 0.1 and 0.5 g/kg of tannic acid. Primary bile acid excretion increased significantly only in rats given a dose of 0.1 g/kg of Polyphenon. This is the first report that documents the changes occurring in fecal steroid excretion induced by oral administration of green tea polyphenol or tannic acid.

Dietary Stearic Acid Reduces Cholesterol Absorption and Increases Endogenous Cholesterol Excretion in Hamsters Fed Cereal-Based Diets

The observation that dietary stearic acid does not raise plasma cholesterol concentration is well documented, although the regulating mechanisms are not completely understood. Therefore, we examined the effect of dietary stearic acid on cholesterol absorption and sterol balance using male Syrian hamsters fed modified NIH-07 cereal-based diets selectively enriched in palmitic acid (16:0), stearic acid (18:0), trans fatty acid (18:1t), cis oleic acid (18:1c) or linoleic acid (18:2). All diets contained 17 g/100 g total fat and 0.05 g/100 g cholesterol; the five fat blends were enriched 30% with the fatty acid of interest above a constant fatty acid background. Cholesterol absorption efficiency was 50-55% in all treatment groups except for the 18:0 group, in which cholesterol absorption was significantly reduced to 21%. Plasma total cholesterol concentration was significantly lower in the 18:0 group compared to the 16:0 group. Fecal neutral steroid excretion was significantly greater in hamsters fed the high 18:0 diet compared to the other treatment groups. After accounting for unabsorbed dietary cholesterol, endogenous cholesterol excretion was about 100% higher in the 18:0 group. Consequently, the calculated rate of whole body cholesterol synthesis was significantly increased by dietary 18:0. Bile acid excretion accounted for only 12-20% of total sterol output by the hamsters in this study. Thus, the data suggest that reduced plasma cholesterol concentration in hamsters fed high 18:0 diets may be influenced by reduced cholesterol absorption and increased excretion of endogenous cholesterol.

Fecal Steroid Excretion Is Increased in Rats by Oral Administration of Gymnemic Acids Contained in Gymnema sylvestre Leaves

Gymnemic acids are the saponins with a triterpenoid structure contained in Gymnema sylvestre leaves and have the hypoglycemic effects. In spite of the cholesterol-binding properties of saponins, the effect of gymnemic acids on cholesterol metabolism has not been elucidated to date. We investigated the effects of gymnemic acids on fecal steroid excretion in rats. Three kinds of extracts from Gymnema sylvestre leaves, extract (GSE), acid precipitate (GSA) and column fractionate (GSF), of which the gymnemagenin (an aglycone of gymnemic acids) concentrations are 58.87, 161.6, and 363.3 mg/g respectively, were used for the experiments. These were administered to rats orally at the dose of 0.05–1.0 g/kg for 22 d. Rats were given free access to water and nonpurified diet without cholesterol, and the differences in fecal excretion of steroids and gymnemic acids were investigated. Although there were no significant effects of GSE, GSA and GSF decreased body weight gain and food intakes in a dose-dependent manner (P < 0.01). GSF (1.0 g/kg) significantly increased fecal excretion of neutral steroids and bile acids in a dose-dependent manner (P < 0.05), especially those of cholesterol and cholic acid (CA)-derived bile acids. The increases in fecal steroid excretion of cholesterol, total neutral steroids, total bile acids and CA-related bile acids were acute and significantly correlated with fecal gymnemagenin levels (r2 = 0.2316–0.9861, P < 0.05). These results demonstrated for the first time that a high dose of gymnemic acids increases fecal cholesterol and CA-derived bile acid excretion. Further studies are needed to clarify the effect of gymnemic acids on cholesterol metabolism.