Fecal Neutral Sterol Excretion Research Articles

Artichoke Extract Lowered Plasma Cholesterol and Increased Fecal Bile Acids in Golden Syrian Hamsters

A study was conducted in hamsters to determine if artichoke leaf extract (ALE) could lower plasma total and non-HDL cholesterol by increasing fecal excretion of neutral bile acids and sterols. Sixty-four Golden Syrian hamsters (8 week old) were fed control diet or a similar diet containing ALE (4.5 g/kg diet) for 6 weeks. No significant changes for total cholesterol, HDL, non-HDL cholesterol triglycerides or fecal neutral sterols and bile acids were found after 21 days for ALE-fed animals compared with controls. But after 42 days, ALE-fed male hamsters had significantly lower total cholesterol (15%), non-HDL cholesterol (30%) and triglycerides (22%) and female hamsters fed ALE showed reductions of 15% for total cholesterol, 29% for non-HDL cholesterol and 29% for triglycerides compared with controls. Total neutral sterol and bile acids concentrations increased significantly by 50% and 53% in fecal samples of ALE fed males, and 82.4% and 25% in ALE fed females compared with controls. The ALE lowered hamster plasma cholesterol levels by a mechanism involving the greater excretion of fecal bile acids and neutral sterols after feeding for 42 days.

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.

Study of directed insilico mutations on polyphenol oxidase to improve enzyme–substrate binding efficiency

7S protein is one of four major storage proteins in soybean. The present study compared the relative cholesterol-lowering activity of the 7S protein with that of total soybean protein isolate (SPI). Forty-eight hamsters were divided into six groups fed non-cholesterol diet or one of five high-cholesterol diets containing 24.2% casein, 12.1–24.2% SPI, 12.1–24.2% 7S protein, respectively. Results showed the 7S protein reduced plasma total cholesterol (TC) by 20–41% while SPI reduced it by 9–16%. 7S protein increased the fecal excretion of neutral sterols by 43–116%, while SPI only had 18–68% increase. 7S protein increased the excretion of total bile acids by 208–367%, while SPI only increased it by 41–86%. 7S protein could not only down regulate gene expression of HMG-CoA reductase but also up regulate gene expression of CYP7A1. It was concluded that dietary 7S protein was more hypocholesterolemic than SPI, mediated by increasing the sterol excretion and decreasing the cholesterol synthesis.

Phytosterol stearate esters elicit similar responses on plasma lipids and cholesterol absorption but different responses on fecal neutral sterol excretion and hepatic free cholesterol in male Syrian hamsters

The dietary impact of specific phytosterols incorporated into phytosterol fatty acid esters has not been elucidated. Therefore, we tested the hypothesis that phytosterol esters containing different sterol moieties (sitosterol, sitostanol, or stigmasterol) but the same fatty acid moiety (stearic acid) produce different effects on cholesterol metabolism. Male Syrian hamsters were fed sitosterol, sitostanol, and stigmasterol stearate esters (25 g/kg diet) in an atherogenic diet containing cholesterol (1.2 g/kg) and coconut oil (80 g/kg). The phytosterol stearates produced no decrease in cholesterol absorption or plasma non-high-density lipoprotein cholesterol despite a reduction in liver free cholesterol in hamsters fed both sitosterol and sitostanol stearate diets. In addition, sitosterol stearate significantly increased fecal esterified and total neutral sterol excretion. Stigmasterol stearate did not differ from control in neutral sterol excretion, plasma lipids, or hepatic lipid concentration. Sitosterol stearate demonstrated the highest level of net intestinal hydrolysis, whereas sitostanol and stigmasterol stearate equivalently demonstrated the lowest. The cholesterol-lowering effect in liver-but not plasma-and the limited presence of fecal free sterols indicate that intact (unhydrolyzed) phytosterol stearates may impact cholesterol metabolism by mechanisms unrelated to the role of free phytosterols. The consumption of phytosterol esters at 2.5% of the diet elicited only modest impacts on cholesterol metabolism, although sitosterol stearate had a slightly greater therapeutic impact by lowering liver free cholesterol and increasing esterified and total neutral sterol fecal excretion, possibly due to a greater level of intestinal hydrolysis.

From blood to gut: direct secretion of cholesterol via transintestinal cholesterol efflux.

The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol-lowering therapies. By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body. For a long time this removal via the hepatobiliary secretion was considered to be the sole route involved in the RCT. However, observations from early studies in animals and humans already pointed towards the possibility of another route. In the last few years it has become evident that a non-biliary cholesterol secretion pathway exists in which the intestine plays a central role. This transintestinal cholesterol efflux (TICE) pathway contributes significantly to the total fecal neutral sterol excretion. Moreover, recent studies have shown that TICE is also sensitive to stimulation. As a consequence, the direct role of cholesterol secretion from blood via TICE makes the intestine a suitable and approachable target for cholesterol removal from the body and possibly reduction of atherosclerosis. In this review, the discovery and recent findings contributing to understanding the mechanism of TICE will be discussed.

Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters

Hawthorn (Crataegus pinnatifida) is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT) activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA) and ursolic acid (UA)) contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE) were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w) cholesterol (control) or the same diet supplemented with (i) 0.37% hawthorn dichloromethane extract, (ii) 0.24% PSE, (iii) hawthorn dichloromethane extract (0.37%) plus PSE (0.24%) or (iv) OA/UA mixture (0.01%) for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL) cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA) enhanced the cholesterol lowering effect of plant sterols.

Dietary cholesterol reverses resistance to diet-induced weight gain in mice lacking Niemann-Pick C1-Like 1

Niemann-Pick C1-Like 1 (NPC1L1) mediates intestinal cholesterol absorption. NPC1L1 knockout (L1-KO) mice were recently shown to be resistant to high-fat diet (HFD)-induced obesity in one study, which was contrary to several other studies. Careful comparison of dietary compositions in these studies implies a potential role of dietary cholesterol in regulating weight gain. To examine this potential, wild-type (WT) and L1-KO mice were fed one of three sets of diets for various durations: (1) a HFD without added cholesterol for 5 weeks; (2) a high-carbohydrate diet with or without added cholesterol for 5 weeks; or (3) a synthetic HFD with or without added cholesterol for 18 weeks. We found that L1-KO mice were protected against diet-induced weight gain only on a diet without added cholesterol but not on a diet containing 0.16% or 0.2% (w/w) cholesterol, an amount similar to a typical Western diet, regardless of the major energy source of the diet. Food intake and intestinal fat absorption were similar between the two genotypes. Intestinal cholesterol absorption was blocked, and fecal cholesterol excretion increased in L1-KO mice. Under all diets, L1-KO mice were protected from hepatosteatosis. In conclusion, increasing dietary cholesterol restores diet-induced weight gain in mice deficient in NPC1L1-dependent cholesterol absorption.

Avaliação sensorial de produtos panificados com adição de farinha de bagaço de maçã

The industrialization process of apple, particularly juice, generates the pomace as the main residue or by-product, whose proper management should be among the priorities of the processing industries. The physicochemical composition of the apple pomace flour obtained in this study consisted of 43% of fiber on a dry basis. Studies on the fibers show that they have a hypocholesterolemic action reducing the digestion and absorption of dietary lipids, increasing the fecal excretion of bile acids and neutral sterols, increasing the production of short-chain fatty acids in the colon, and decreasing the percentage of primary bile acids. The objective of this study was to evaluate sensorially bakery products added with apple pomace flour to show that the apple pomace flour can be a potential alternative source of dietary fibers in bakery products.

Ezetimibe stimulates faecal neutral sterol excretion depending on abcg8 function in mice

Ezetimibe stimulates faecal neutral sterol (FNS) excretion in mice, which cannot be explained by cholesterol absorption inhibition alone. We investigated whether these effects are mediated via the sterol exporter ATP binding cassette transporter G8 (abcg8). Ezetimibe increased FNS excretion 2.7-fold in WT mice and 1.5-fold in abcg8 −/− mice, without affecting biliary cholesterol secretion. Daily FNS excretion exceeded the sum of dietary cholesterol intake and biliary secretion by about 60%. Ezetimibe enhanced this ‘extra’ FNS excretion by 3.5-fold and 1.5-fold in wildtype (WT) and abcg8 −/− mice, respectively. Ezetimibe stimulates fecal sterol excretion of non-biliary and non-dietary origin, probably through stimulation of trans-intestinal cholesterol excretion. We show that this effect depends on intact abcg8 function.

Voluntary exercise increases cholesterol efflux but not macrophage reverse cholesterol transport in vivo in mice

Physical exercise beneficially impacts on the plasma lipoprotein profile as well as on the incidence of cardiovascular events and is therefore recommended in primary and secondary prevention strategies against atherosclerotic cardiovascular disease. However, the underlying mechanisms of the protective effect of exercise remain largely unknown. Therefore, the present study tested the hypothesis that voluntary exercise in mice impacts on cholesterol efflux and in vivo reverse cholesterol transport (RCT). After two weeks of voluntary wheel running (average 10.1 ± 1.4 km/day) plasma triglycerides were lower (p < 0.05), while otherwise lipid and lipoprotein levels did not change. Macrophage cholesterol efflux towards plasma was significantly increased in running (n = 8) compared to sedentary (n = 6) mice (14.93 ± 1.40 vs. 12.33 ± 2.60%, p < 0.05). In addition, fecal excretion of bile acids (3.86 ± 0.50 vs. 2.90 ± 0.51 nmol/d, p = 0.001) and neutral sterols (2.75 ± 0.43 vs. 1.94 ± 0.22 nmol/d, p < 0.01) was significantly higher in running mice. However, RCT from macrophages to feces remained essentially unchanged in running mice compared with sedentary controls (bile acids: 3.2 ± 1.0 vs. 2.9 ± 1.1 % of injected dose, n.s.; neutral sterols: 1.4 ± 0.7 vs. 1.1 ± 0.5 % injected dose, n.s.). Judged by the plasma lathosterol to cholesterol ratio, endogenous cholesterol synthesis was increased in exercising mice (0.15 ± 0.03 vs. 0.11 ± 0.02, p < 0.05), while the hepatic mRNA expression of key transporters for biliary cholesterol (Abcg5/g8, Sr-bI) as well as bile acid (Abcb11) and phospholipd (Abcb4) excretion did not change. These data indicate that the beneficial effects of exercise on cardiovascular health include increased cholesterol efflux, but do not extend to other components of RCT. The increased fecal cholesterol excretion observed in running mice is likely explained by higher endogenous cholesterol synthesis, however, it does not reflect increased RCT in the face of unchanged expression of key transporters for biliary sterol secretion.

Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid

A mutation in NPC1 leads to sequestration of unesterified cholesterol in the late endosomal/lysosomal compartment of every cell culminating in the development of pulmonary, hepatic, and neurodegenerative disease. Acute administration of 2-hydroxypropyl-beta-cyclodextrin (CYCLO) rapidly overcomes this transport defect in both the 7-day-old pup and 49-day-old mature npc1(-/-) mouse, even though this compound is cleared from the body and plasma six times faster in the mature mouse than in the neonatal animal. The liberated cholesterol flows into the cytosolic ester pool, suppresses sterol synthesis, down-regulates SREBP2 and its target genes, and reduces expression of macrophage-associated inflammatory genes. These effects are seen in the liver and brain, as well as in peripheral organs like the spleen and kidney. Only the lung appears to be resistant to these effects. Forty-eight h after CYCLO administration to the 49-day-old animals, fecal acidic, but not neutral, sterol output increases, whole-animal cholesterol burden is reduced, and the hepatic and neurological inflammation is ameliorated. However, lifespan is extended only when the CYCLO is administered to the 7-day-old animals. These studies demonstrate that CYCLO administration acutely reverses the cholesterol transport defect seen in the NPC1 mouse at any age, and this reversal allows the sequestered sterol to be excreted from the body as bile acid.

The liver-selective thyromimetic T-0681 influences reverse cholesterol transport and atherosclerosis development in mice.

BackgroundLiver-selective thyromimetics have been reported to efficiently reduce plasma cholesterol through the hepatic induction of both, the low-density lipoprotein receptor (LDLr) and the high-density lipoprotein (HDL) receptor; the scavenger receptor class B type I (SR-BI). Here, we investigated the effect of the thyromimetic T-0681 on reverse cholesterol transport (RCT) and atherosclerosis, and studied the underlying mechanisms using different mouse models, including mice lacking LDLr, SR-BI, and apoE, as well as CETP transgenic mice.Methodology/Principal FindingsT-0681 treatment promoted bile acid production and biliary sterol secretion consistently in the majority of the studied mouse models, which was associated with a marked reduction of plasma cholesterol. Using an assay of macrophage RCT in mice, we found T-0681 to significantly increase fecal excretion of macrophage-derived neutral and acidic sterols. No positive effect on RCT was found in CETP transgenic mice, most likely due to the observed decrease in plasma CETP mass. Studies in SR-BI KO and LDLr KO mice suggested hepatic LDLr to be necessary for the action of T-0681 on lipid metabolism, as the compound did not have any influence on plasma cholesterol levels in mice lacking this receptor. Finally, prolonged treatment with T-0681 reduced the development of atherosclerosis by 60% in apoE KOs on Western type diet. In contrast, at an earlier time-point T-0681 slightly increased small fatty streak lesions, in part due to an impaired macrophage cholesterol efflux capacity, when compared to controls.Conclusions/SignificanceThe present results show that liver-selective thyromimetics can promote RCT and that such compounds may protect from atherosclerosis partly through induction of bile acid metabolism and biliary sterol secretion. On-going clinical trials will show whether selective thyromimetics do prevent atherosclerosis also in humans.

Hypocholesterolemic activity of onion is mediated by enhancing excretion of fecal sterols in hamsters

Onion has been shown to favorably modify the lipoprotein profile. However, research on its underlying mechanism is lacking. The present study investigated the interaction of dietary onion powder with the protein expression of key receptors and enzymes involved in cholesterol metabolism. Thirty-six male hamsters were randomly divided into three groups and fed a high-cholesterol control diet or the two experimental diets supplemented with 1% onion powder (OP-1) or 5% onion powder (OP-5), for a period of 8 weeks. It was found that onion dose-dependently decreased plasma total cholesterol (TC) level. The change in plasma lipoprotein profile was accompanied by a greater excretion of both fecal neutral and acidic sterols. Western blot analysis revealed that onion up-regulated sterol regulatory element binding protein 2 (SREBP-2), liver X receptor alpha (LXRα) and cholesterol-7α-hydroxylase (CYP7A1) with no effect on 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and LDL receptor (LDL-R). It was concluded that the hypocholesterolemic activity of onion powder was mediated by enhancement of fecal sterol excretion and up-regulation of LXRα and CYP7A1.

Hypocholesterolemic Effects of Nutraceuticals Produced from the Red Microalga Porphyridium sp. in Rats

Red microalgae contain functional sulfated polysaccharides (containing dietary fibers), polyunsaturated fatty acids, zeaxanthin, vitamins, minerals, and proteins. Studies in rat models support the therapeutic properties of algal biomass and isolated polysaccharides. Algal products incorporated into rat diets were found to significantly improve total serum cholesterol, serum triglycerides, hepatic cholesterol levels, HDL/LDL ratios and increased fecal excretion of neutral sterols and bile acids. Morphological and metabolic changes were induced by consumption of algal products. These results suggest that red microalgae can be used as potent hypocholesterolemic agents, and they support the potential use of red microalgae as novel nutraceuticals.

Peroxisome proliferator-activated receptor delta activation leads to increased transintestinal cholesterol efflux

Peroxisome proliferator-activated receptor delta (PPARdelta) is involved in regulation of energy homeostasis. Activation of PPARdelta markedly increases fecal neutral sterol secretion, the last step in reverse cholesterol transport. This phenomenon can neither be explained by increased hepatobiliary cholesterol secretion, nor by reduced cholesterol absorption. To test the hypothesis that PPARdelta activation leads to stimulation of transintestinal cholesterol efflux (TICE), we quantified it by intestine perfusions in FVB mice treated with PPARdelta agonist GW610742. To exclude the effects on cholesterol absorption, mice were also treated with cholesterol absorption inhibitor ezetimibe or ezetimibe/GW610742. GW601742 treatment had little effect on plasma lipid levels but stimulated both fecal neutral sterol excretion ( approximately 200%) and TICE ( approximately 100%). GW610742 decreased intestinal Npc1l1 expression but had no effect on Abcg5/Abcg8. Interestingly, expression of Rab9 and LIMPII, encoding proteins involved in intracellular cholesterol trafficking, was increased upon PPARdelta activation. Although treatment with ezetimibe alone had no effect on TICE, it reduced the effect of GW610742 on TICE. These data show that activation of PPARdelta stimulates fecal cholesterol excretion in mice, primarily by the two-fold increase in TICE, indicating that this pathway provides an interesting target for the development of drugs aiming at the prevention of atherosclerosis.

Sorghum distillers dried grain lipid extract increases cholesterol excretion and decreases plasma and liver cholesterol concentration in hamsters

Grain sorghum is a rich source of phytochemicals. In this study, male hamsters were fed AIN-93M diets supplemented with a hexane-extractable lipid fraction from sorghum distillers dried grains with solubles (DDGS). Diets contained 0.0%, 0.5%, 1.0%, and 5.0% (w/w) DDGS lipid extract. After 4 wk, the 5.0% DDGS lipids group had significantly lower plasma non-HDL cholesterol and liver esterified cholesterol concentration. Faecal neutral sterol (i.e., cholesterol) excretion was significantly higher in the 5.0% DDGS lipids group compared to the other treatments (66% higher compared to controls). Bile acid excretion was not affected by DDGS lipid intake. Faecal cholesterol excretion was negatively correlated with liver cholesterol concentration ( r = −0.97, P = 0.026), and liver cholesterol concentration was directly correlated with plasma total cholesterol concentration ( r = 0.96, P = 0.041). Thus, lipid extract of sorghum DDGS exhibited cholesterol-lowering properties due, at least in part, to increased cholesterol excretion from the body and could provide health benefits when incorporated into human diets.

Effect of White Wheat Bread Containing Sugar Beet Fiber on Serum Lipids and Hepatic mRNA in Rats Fed on a Cholesterol-Free Diet

We examined the effects of white wheat bread powder (BP) and white wheat bread powder containing sugar beet fiber (BBP) on serum cholesterol. The total cholesterol (-11%, -16%), HDL-cholesterol (-12%, -11%), non-HDL-cholesterol (-9%, -18%) and triacylglycerol (-44%, -58%) concentrations in the BP and BBP groups, respectively, were significantly different from those in the control group. The fecal excretion of neutral sterols in the BP and BBP groups and of acidic sterols in the BBP group was significantly higher than that in the control group. The hepatic cholesterol 7alpha-hydroxylase (CYP7A1) mRNA level in the BP and BBP groups was significantly higher than that in the control group. The cecal total short-chain fatty acid concentrations in the BBP group were significantly higher than those in the control group. These results indicate that the observed changes in serum lipid levels in the BP and BBP groups were due to the increased fecal lipid and CYP7A1 mRNA levels.

Reduced fecal sterol excretion in subjects with familial hypoalphalipoproteinemia

Background Fecal bile acid and neutral sterol excretion are the obligate endpoints of the reverse cholesterol transport pathway (RCT). In studies in mice, no evidence was found for a relation between HDL-cholesterol (HDL-c) levels and fecal sterol excretion. In this study, we have evaluated this relationship in patients with isolated low HDL-c versus controls. Results Fecal sterol excretion was studied in 12 subjects with familial hypoalphalipoproteinemia (FHA) and 11 healthy controls. Compared to the controls (8.9 ± 6.3 mg/kg/day), neutral sterol excretion was significantly lower in the FHA group (4.0 ± 2.4 mg/kg/day). Fecal bile acid excretion showed a similar pattern. Across the groups, a strong positive correlation between HDL-c and fecal neutral sterol excretion was found ( r = 0.53; p = 0.01). Conclusions Isolated low HDL-c levels in humans are associated with reduced fecal sterol excretion suggesting that in humans HDL regulates the final step in the RCT pathway at low HDL-c levels.

Abstract: S1-6 CHOLESTEROL ABSORPTION AND SYNTHESIS MARKERS FOR CARDIOVASCULAR DISEASE RISK.

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 μmol/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 (<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.

Hypocholesterolemic effect of Nostoc commune var. sphaeroides Kützing, an edible blue-green alga

Intake of an edible blue-green alga Nostoc commune var. sphaeroides Kützing (N. Commune) has been shown to lower plasma total cholesterol concentration, but the mechanisms behind the hypocholesterolemic effect have not been elucidated. To elucidate the mechanisms underlying the cholesterol-lowering effect of N. commune in mice. Male C57BL/6J mice were fed the AIN-93 M diet supplemented with 0 or 5% (wt/wt) dried N. Commune for 4 weeks. Lipid levels in the plasma and liver, intestinal cholesterol absorption and fecal sterol excretion were measured. Expression of hepatic and intestinal genes involved in cholesterol metabolism was evaluated by quantitative realtime PCR. N. commune supplementation significantly reduced total plasma cholesterol and triglyceride concentrations by approximately 20% compared to controls. Intestinal cholesterol absorption was significantly decreased, while fecal neutral sterol output was significantly increased in N. commune-fed mice. mRNA levels of the cholesterol transporters such as Niemann Pick C1 Like 1, scavenger receptor class B type 1, ATP-binding cassette transporters G5 and A1 in small intestine were not significantly different between two groups. Hepatic lipid contents including total cholesterol, triglyceride and free cholesterol in N. commune-fed mice were not significantly altered. However, the expression of cholesterol modulating genes including sterol regulatory element binding protein-2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase were significantly increased in mice fed N. commune. N. commune supplementation exerted a hypocholesterolemic effect in mice, largely in part, by reducing intestinal cholesterol absorption and promoting fecal neutral sterol excretion.