Fecal Neutral Sterol Research Articles

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.

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.

A Diet Rich in Leafy Vegetable Fiber Improves Cholesterol Metabolism in High-Cholesterol Fed Rats

In the present study, the hypocholesterolemic effect of leaf vegetable (Jew's mallow) was studied in high-cholesterol fed rats. The animals were fed diets supplemented with cholesterol (0.25%) for 4 weeks. Leaf vegetable diet produced an important hypocholesterolemic action: it led to a significant lowering (p<0.05) of cholesterol in the plasma and liver, as well as of the atherogenic index and a significant increase (p<0.05) in cecal short chain fatty acids, with respect to the control group. Concurrently, total fecal neutral sterols in the excretion increased (p<0.05) and apparent absorption of dietary cholesterol was significantly depressed (-58%). The consumption of leaf vegetable (Jew's mallow) with a hypercholesterolemic diet improved the lipidemic profile and increased excretion of the total cholesterol end-products.

Potato and soy peptides alter caecal fermentation and reduce serum non‐HDL cholesterol in rats fed cholesterol

AbstractWe examined the effect of potato peptides (PPC) in rats fed a cholesterol‐enriched diet, in comparison with two cholesterol‐enriched diets containing soy peptides (SPC) or casein (CNC), and a cholesterol‐free diet containing casein (CN) for 4 weeks. The serum non‐high‐density lipoprotein (HDL) cholesterol level was lower in the PPC‐ (–18.39%) and SPC‐fed (–32.76%) groups (p &lt;0.05) than in the CNC‐fed group at the end of the feeding period. The low‐density lipoprotein receptor mRNA level in the PPC‐fed group, and cholesterol 7α‐hydroxylase and scavenger receptor class B type 1 mRNA levels in the SPC‐fed group, were higher (p &lt;0.05) than in the CN‐ and CNC‐fed groups. Faecal neutral sterol and caecal short‐chain fatty acid concentrations in the PPC‐ and SPC‐fed groups were higher (p &lt;0.05) than in the CN‐ and CNC‐fed groups. The faecal total acidic sterol concentration was higher in the SPC‐fed group than in the CN‐ and PPC‐fed groups. Caecal anaerobe and Bifidobacterium populations were higher (p &lt;0.05) in the PPC‐ and SPC‐fed groups than in the CN‐fed group. This study suggests that potato peptides, as soy peptides, alter caecal fermentation and steroid absorption and reduce the serum non‐HDL cholesterol level in rats fed cholesterol.

Red Yeast Rice Increases Excretion of Bile Acids in Hamsters

To investigate the hypocholesterolemic activity of red yeast rice (RYR) and its underlying mechanism. Three groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR (0.1RYR) or 0.3% RYR (0.3RYR). Blood (0.5 mL) was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0, 3, and 6. Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography. Plasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by 11% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, liver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7alpha-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K. It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 3-4 folds compared with the control value. Hypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.

Fish Oil Promotes Macrophage Reverse Cholesterol Transport in Mice

Fish oil (FO), and specifically omega 3 fatty acids, has favorable effects on cardiovascular outcomes. The aim of this study was to investigate the effects of FO on the process of macrophage reverse cholesterol transport (RCT) in an in vivo mouse model. C57BL/6J mice were fed a FO diet, whereas control mice were fed diets containing alternative sources of fats, soybean oil (SO), and coconut oil (CO) for 4 weeks. Macrophage RCT was assessed by injecting [(3)H]cholesterol-labeled J774 macrophages intraperitoneally into mice. After 48 hours, tissues were harvested and feces were collected. An increase in the excretion of macrophage-derived [(3)H]-tracer recovered in fecal neutral sterols for FO-fed mice was observed (273% versus SO and 182% versus CO). FO also decreased [(3)H]-tracer in hepatic cholesteryl ester compared to SO and CO by 76% and 56%, respectively. To specifically determine the effect of FO on the fate of HDL-derived cholesterol, mice fed FO or SO diets were injected with HDL labeled with [(3)H]cholesteryl oleate, and the disappearance of [(3)H]-tracer from blood and its excretion in feces was measured. There was no significant difference in the fractional catabolic rate of [(3)H]cholesteryl oleate-HDL between the 2 groups. However, there was a 242% increase in the excretion of HDL-derived [(3)H]-tracer recovered in fecal neutral sterols in FO-fed mice, concordant with significantly increased expression of hepatic Abcg5 and Abcg8 mRNA. As measured by this tracer-based assay, FO promoted reverse cholesterol transport, primarily by enhancement of the hepatic excretion of macrophage-derived and HDL-derived cholesterol.

Activation of the Liver X Receptor Stimulates Trans-intestinal Excretion of Plasma Cholesterol

Recent studies have indicated that direct intestinal secretion of plasma cholesterol significantly contributes to fecal neutral sterol loss in mice. The physiological relevance of this novel route, which represents a part of the reverse cholesterol transport pathway, has not been directly established in vivo as yet. We have developed a method to quantify the fractional and absolute contributions of several cholesterol fluxes to total fecal neutral sterol loss in vivo in mice, by assessing the kinetics of orally and intravenously administered stable isotopically labeled cholesterol combined with an isotopic approach to assess the fate of de novo synthesized cholesterol. Our results show that trans-intestinal cholesterol excretion significantly contributes to removal of blood-derived free cholesterol in C57Bl6/J mice (33% of 231 micromol/kg/day) and that pharmacological activation of LXR with T0901317 strongly stimulates this pathway (63% of 706 micromol/kg/day). Trans-intestinal cholesterol excretion is impaired in mice lacking Abcg5 (-4%), suggesting that the cholesterol transporting Abcg5/Abcg8 heterodimer is involved in this pathway. Our data demonstrate that intestinal excretion represents a quantitatively important route for fecal removal of neutral sterols independent of biliary secretion in mice. This pathway is sensitive to pharmacological activation of the LXR system. These data support the concept that the intestine substantially contributes to reverse cholesterol transport.

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.

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.

The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis

Reverse cholesterol transport (RCT) is a term used to describe the efflux of excess cellular cholesterol from peripheral tissues and its return to the liver for excretion in the bile and ultimately the feces. It is believed to be a critical mechanism by which HDL exert a protective effect on the development of atherosclerosis. In this paradigm, cholesterol is effluxed from arterial macrophages to extracellular HDL-based acceptors through the action of transporters such as ABCA1 and ABCG1. After efflux to HDL, cholesterol may be esterified in the plasma by the enzyme lecithin:cholesterol acyltransferase and is ultimately transported from HDL to the liver, either directly via the scavenger receptor BI or after transfer to apolipoprotein B-containing lipoproteins by the cholesteryl ester transfer protein. Methods for assessing the integrated rate of macrophage RCT in animals have provided insights into the molecular regulation of the process and suggest that the dynamic rate of macrophage RCT is more strongly associated with atherosclerosis than the steady-state plasma concentration of HDL cholesterol. Promotion of macrophage RCT is a potential therapeutic approach to preventing or regressing atherosclerotic vascular disease, but robust measures of RCT in humans will be needed in order to confidently advance RCT-promoting therapies in clinical development.

Investigations on the Effect of Flavonoids from Banana, Musa Paradisiaca L. on Lipid Metabolism in Rats

Oral administration of flavonoids extracted from unripe fruits of Musa paradisiaca showed significant hypolipidemic activities in male rats (Sprague Dawley strain) at a dose of 1 mg/100 g body weight (BW)/day. Concentrations of cholesterol, phospholipids, free fatty acids, and triglycerides showed significant decrease in the serum, liver, kidney, and brain of experimental animals. HMG CoA reductase activity was found to be enhanced, while activities of glucose-6-phosphate dehydrogenase and malate dehydrogenase were significantly reduced. Activities of lipoprotein lipase and plasma LCAT showed significant enhancement. A significant increase in the concentrations of hepatic and fecal bile acids and fecal neutral sterols was also observed indicating a higher rate of degradation of cholesterol. The present study indicates that although there is an increase in the rate of synthesis of cholesterol in the liver, the process of degradation exceeds the rate of synthesis.

A Rice Bran Oil Diet Improves Lipid Abnormalities and Suppress Hyperinsulinemic Responses in Rats with Streptozotocin/Nicotinamide-Induced Type 2 Diabetes

The aim of this study was to determine the effects of rice bran oil (RBO) on lipid metabolism and insulin resistance in rats with streptozotocin/nicotinamide-induced type 2 diabetes mellitus (T2DM). Rats were divided into two groups: the control group (15% soybean oil, contains 0 g γ-oryzanol and 0 g γ-tocotrienol/150 g oil for 5 weeks) and the RBO group (15% RBO, contains 5.25 g γ-oryzanol and 0.9 g γ-tocotrienol/150 g oil for 5 weeks). Compared with the control group, the RBO group had a lower plasma nonesterified fatty acid concentration, ratio of total to high-density-lipoprotein cholesterol, hepatic cholesterol concentration, and area under the curve for insulin. The RBO group had a higher high-density-lipoprotein cholesterol concentration and greater excretion of fecal neutral sterols and bile acid than did the control group. RBO may improve lipid abnormalities, reduce the atherogenic index, and suppress the hyperinsulinemic response in rats with streptozotocin/nicotinamide-induced T2DM. In addition, RBO can lead to increased fecal neutral sterol and bile acid excretion.

무청분말이 콜레스테롤식이를 공급한 흰쥐의 장기능 및 분변 중 중성지질 및 Sterol 배설에 미치는 영향

본 연구에서는 고콜레스테롤 흰쥐에 무청파우더를 공급함으로써 분변을 통한 지질배설과 장기능 개선에 미치는 효과와 그 작용기전을 규명하고자 간조직의 UDP-glucuronyl transferase 활성변화와 분변중의 지질 및 sterol류의 조성을 관찰하였다. 실험동물은 체중 100 g내외의 Sprague-Dawley종 수컷 흰쥐를 이용하였으며, 정상군과 고콜레스테롤 식이 실험군으로 나눈 후 정상군은 다시 무청파우더를 공급하지 않은 군(N group), 무청파우더를 공급한 군(NR group)으로 나누고 고콜레스테롤 식이 실험군은 무청파우더를 공급하지 않은 군(HC group)과 무청파우더를 각각 2.5%(HRL group), 5%(HRM group), 10%(HRH group)씩 공급한 군으로 나누었다. 식이와 식수는 자유섭식 시켰으며, 4주 간 사육한 후 희생시켰다. 분변량은 무청공급군들에서 무청의 공급량이 증가할수록 많은 배변량을 보였다. 수분함량 역시 HC군에 비해 무청공급군들에서 많은 함량을 보였다. 분변중의 총지질, 총콜레스테롤 및 TG 함량은 HC군에 비해 무청공급군들에서 현저하게 증가되었다. 분변중의 bile acid 함량은 HC군에 비해 HRM 및 HRH군에서 2.3배 및 2.7배씩 각각 증가되었다. 분변중의 중성 스테롤류인 cholesterol, coprostanol, coprostanone 함량은 HC군에 비해 다소 높은 경향이었다. 간 microsome의 UDPGT의 활성은 HC군에 비해 HRH군에서 38% 유의적으로 증가되어 가장 높은 활성을 나타내었다. 이상의 결과를 통해 무청은 고콜레스테롤 식이 흰쥐에서 간조직의 UDPGT 활성의 증가로 담즙산의 흡수를 지연시킴으로써 고콜레스테롤 섭취 시 분변중으로 총지질, 총콜레스테롤, 중성지방, 중성스테롤 및 산성스테롤인 담즙산의 배설을 증가시키는 작용을 나타내었고, 따라서 장기능 및 지질대사 개선을 위한 우수 물질임을 알 수 있었다.

Inhibiting intestinal NPC1L1 activity prevents diet-induced increase in biliary cholesterol in Golden Syrian hamsters

Niemann-Pick C1-like 1 (NPC1L1) facilitates the uptake of sterols into the enterocyte and is the target of the novel cholesterol absorption inhibitor, ezetimibe. These studies used the Golden Syrian hamster as a model to delineate the changes in the relative mRNA expression of NPC1L1 and other proteins that regulate sterol homeostasis in the enterocyte during and following cessation of ezetimibe treatment and also to address the clinically important question of whether the marked inhibition of cholesterol absorption alters biliary lipid composition. In hamsters fed a low-cholesterol, low-fat basal diet, the abundance of mRNA for NPC1L1 in the small intestine far exceeded that in other regions of the gastrointestinal tract, liver, and gallbladder. In the first study, female hamsters were fed the basal diet containing ezetimibe at doses up to 2.0 mg.day(-1).kg body wt(-1). At this dose, cholesterol absorption fell by 82%, fecal neutral sterol excretion increased by 5.3-fold, and hepatic and intestinal cholesterol synthesis increased more than twofold, but there were no significant changes in either fecal bile acid excretion or biliary lipid composition. The ezetimibe-induced changes in intestinal cholesterol handling were reversed when treatment was withdrawn. In a second study, male hamsters were given a diet enriched in cholesterol and safflower oil without or with ezetimibe. The lipid-rich diet raised the absolute and relative cholesterol levels in bile more than fourfold. This increase was largely prevented by ezetimibe. These data are consistent with the recent finding that ezetimibe treatment significantly reduced biliary cholesterol saturation in patients with gallstones.

A New Twist in the Cholesterol Metabolism-Based Enterohepatic Connection

A New Twist in the Cholesterol Metabolism-Based Enterohepatic Connection

Mechanism for the Cholesterol-Lowering Action of Egg White Protein in Rats

Eggs are a popular source of dietary cholesterol, but their consumption does not necessarily result in an increased serum cholesterol concentration. We investigated the cholesterol-lowering activity of egg white protein (EWP) and its potential mechanism in rats. The consumption of EWP resulted in a decreased concentration of cholesterol in the serum, liver and intestinal mucosa. The excretion of fecal neutral sterols and bile acids was greater by rats fed with EWP than by those fed with casein. The ratio of cholesterol and bile acids in the micellar phase to those in the solid phase was lower in the intestinal contents from rats fed with EWP than from those fed with casein. These results suggest that the cholesterol-lowering activity of EWP can be attributed to lowering the cholesterol absorption by intervening in the micellar formation in the intestines.

Targeted Depletion of Hepatic ACAT2-driven Cholesterol Esterification Reveals a Non-biliary Route for Fecal Neutral Sterol Loss

Deletion of acyl-CoA:cholesterol O-acyltransferase 2 (ACAT2) in mice results in resistance to diet-induced hypercholesterolemia and protection against atherosclerosis. Recently, our group has shown that liver-specific inhibition of ACAT2 via antisense oligonucleotide (ASO)-mediated targeting likewise limits atherosclerosis. However, whether this atheroprotective effect was mediated by: 1) prevention of packaging of cholesterol into apoB-containing lipoproteins, 2) augmentation of nascent HDL cholesterol secretion, or 3) increased hepatobiliary sterol secretion was not examined. Therefore, the purpose of these studies was to determine whether hepatic ACAT2 is rate-limiting in all three of these important routes of cholesterol homeostasis. Liver-specific depletion of ACAT2 resulted in reduced packaging of cholesterol into apoB-containing lipoproteins (very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein), whereas high density lipoprotein cholesterol levels remained unchanged. In the liver of ACAT2 ASO-treated mice, cholesterol ester accumulation was dramatically reduced, yet there was no reciprocal accumulation of unesterified cholesterol. Paradoxically, ASO-mediated depletion of hepatic ACAT2 promoted fecal neutral sterol excretion without altering biliary sterol secretion. Interestingly, during isolated liver perfusion, ACAT2 ASO-treated livers had augmented secretion rates of unesterified cholesterol and phospholipid. Furthermore, we demonstrate that liver-derived cholesterol from ACAT2 ASO-treated mice is preferentially delivered to the proximal small intestine as a precursor to fecal excretion. Collectively, these studies provide the first insight into the hepatic itinerary of cholesterol when cholesterol esterification is inhibited only in the liver, and provide evidence for a novel non-biliary route of fecal sterol loss.

Nostoc commune var sphaeroides Kutzing, a blue‐green alga, lowers plasma cholesterol levels by promoting fecal neutral sterol excretion in mice

Intake of Nostoc commune var sphaeroides Kützing (N. Commune) has been shown to lower plasma cholesterol levels in rats, but the mechanisms behind the hypocholesterolemic effect have not been elucidated. To elucidate the mechanisms underlying the cholesterol‐lowering effect of N. commune, male C57BL/6 mice were fed the AIN93‐M diet with or without 5% whole N. Commune (wt/wt) supplementation for 4 weeks. N. commune supplementation significantly reduced total plasma cholesterol concentration by ~30 percent compared to controls (P = 0.0049). Hepatic lipids in N. commune fed mice were not significantly altered. However, quantitative Realtime PCR analysis revealed the expression of genes encoding cholesterol 7α‐hydroxylase, sterol regulatory element binding protein 2, and 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase was significantly decreased in mice fed N. commune (P &lt; 0.030). Fecal neutral sterol output, measured by gas chromatography, increased 2‐fold in N. commune‐fed mice, while acidic sterol output remained unchanged. In addition, N. commune supplementation drastically altered mouse intestinal flora populations, demonstrated by denaturing gradient gel electrophoresis. In conclusion, N. commune supplementation exerted a hypocholesterolemic effect, largely in part, by promoting fecal neutral sterol excretion and by modifying the microflora of the intestinal environment.

Dietary plant sterols regulate genes involved in cholesterol metabolism in mouse liver but not intestine

Dietary plant sterols reduce intestinal cholesterol absorption, but their role in the modification of genes involved in cholesterol transport and metabolism is uncertain. Several intestinal genes and transcription factors are candidates for regulation by plant sterols. We tested the hypothesis that dietary plant sterols regulate gene expression of putative sterol transporters in the small intestine. Male C57BL/6 mice were fed modified versions of the AIN‐93M purified rodent diet with either stigmasterol or sitosterol at 3.94 g/kg diet to reflect the 2 g/day recommendation for humans, based on a 2000 kcal diet. Total RNA was extracted from the duodenum and liver of each mouse and NPC1L1, SRBI, SREBP‐2, HMG CoA Reductase, PPARδ, ABCA1, and ABCG5 mRNA was quantified by real time PCR. Fecal neutral sterol and bile acid output, gallbladder bile, plasma and liver lipids were also quantified. While plant sterols had no effect on plasma lipids or gene expression in the intestine, liver lipids and gene expression of SREBP‐2, HMG CoA Reductase, and ABCA1 in the liver of mice fed plant sterols were significantly reduced compared to controls. Furthermore, sitosterol—and, to a lesser extent, stigmasterol—significantly increase fecal neutral sterol excretion. These data indicate that not only do individual plant sterols increase neutral sterol excretion, but they also play a role in regulating the expression of cholesterol homeostasis genes in the liver. [Supported by USDA‐NRI Competitive Grant No. 2007‐35200‐18298]