Fecal Neutral Sterol Excretion Research Articles

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.

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.

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.

Potato and Soy Peptide Diets Modulate Lipid Metabolism in Rats

Dietary plant and animal peptides have been shown to reduce serum lipids. However, the potential of food-derived peptides has yet to be fully elucidated. We investigated the physiological importance of potato peptides in rats fed on a cholesterol-free diet containing 20% potato peptides (PP), when compared with two diets containing either 20% casein (CN) or 20% soy peptides (SP). The high-density lipoprotein (HDL)-cholesterol (+13.8%) and serum triglyceride (-38%) concentrations in the PP-fed group, non-HDL-cholesterol level in the PP- (-22.5%) and SP- (-15.7%) fed groups, and serum total cholesterol concentration (-12%) in the SP-fed group, were significantly different from the control group at the end of the experiment. The fecal excretion of neutral and acidic sterols was higher in the PP- and SP-fed groups, respectively, relative to the control group. These results indicate that the observed changes in the serum cholesterol levels in rats fed on soy and potato peptide appear to have been due to different mechanisms.

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 < 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]

Conjugated and non-conjugated octadecaenoic acids affect differently intestinal acyl coenzyme A: Cholesterol acyltransferase activity

We investigated the relative hypocholesterolemic activity of linoleic acid (LA), conjugated linoleic acid (CLA), α-linolenic acid (LN) and conjugated linolenic acid (CLN) in hamsters. Five groups of hamsters ( n = 10 each) were fed either the control diet or one of the four fatty acids-supplemented diets for 6 weeks. Results demonstrated that the four octadecaenoic acids decreased plasma cholesterol differently, with CLA being the most effective. Western blotting and RT-PCR analysis demonstrated that the four octadecaenoic acids had no effect on sterol regulatory element binding protein-2 (SREBP-2), liver X receptor (LXR), 3-hydroxy-3-methylglutary-CoA reductase (HMGR), LDL receptor (LDLR), and cholesterol-7α-hydroxylase (CYP7A1). However, the four octadecaenoic acids increased the excretion of fecal neutral sterols with CLA being most effective followed by LN, LA and CLN, suggesting they all differentially affect cholesterol absorption. Dietary CLA was associated with the least intestinal acyl coenzyme A: cholesterol acyltransferase (ACAT) activity followed by LN, LA and CLN in a decreasing trend. Since esterification of cholesterol is catalyzed by intestinal ACAT, and is a rate-limiting step in cholesterol absorption, it was concluded that the varying effects of CLA, LN, LA and CLN on blood cholesterol were mediated, at least in part, by their inhibition on intestinal ACAT activity.

Fenofibrate reduces intestinal cholesterol absorption via PPARα-dependent modulation of NPC1L1 expression in mouse

Fibrates, including fenofibrate, exert their biological effects by binding peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily of ligand-activated transcription factors. Treatment with PPARalpha agonists enhances fatty acid oxidation, decreases plasma triglycerides, and may promote reverse cholesterol transport. In addition, fibrate administration can reduce intestinal cholesterol absorption in patients, although the molecular mechanism for this effect is unknown. Because Niemann-Pick C1-Like 1 (NPC1L1) is already known to be a critical protein for cholesterol absorption, we hypothesized that fenofibrate might modulate NPC1L1 expression to alter intestinal cholesterol transport. Here, we find that fenofibrate-treated wild-type mice have decreased fractional cholesterol absorption (35-47% decrease) and increased fecal neutral sterol excretion (51-83% increase), which correspond to decreased expression of NPC1L1 mRNA and protein (38-66% decrease) in the proximal small intestine. These effects of fenofibrate are dependent on PPARalpha, as Ppar alpha-knockout mice fail to respond like wild-type littermates. Fenofibrate affects the ezetimibe-sensitive pathway and retains the ability to decrease cholesterol absorption and NPC1L1 mRNA expression in chow-fed liver X receptor alpha/beta-double-knockout mice and high-cholesterol- or cholic acid-fed wild-type mice. These data demonstrate that fenofibrate specifically acts via PPARalpha to decrease cholesterol absorption at the level of intestinal NPC1L1 expression.

Heat‐Moisture Treatment of High‐Amylose Corn Starch Increases Dietary Fiber Content and Lowers Plasma Cholesterol in Ovariectomized Rats

The effect of dietary high-amylose corn starch (HACS) of varying dietary fiber (DF) content on plasma cholesterol was examined in ovariectomized (OVX) rats. Gelatinized normal corn starch (G-CS) was used as a reference. OVX rats were fed a fiber-free purified diet containing G-CS, HACS, gelatinized high-amylose corn starch (G-HACS), or heat-moisture treated HACS (HM-HACS) at 400 g starch/kg diet for 21 d. The DF content of G-CS, HACS, G-HACS, and HM-HACS measured by the AOAC method was 0.1, 19.3, 2.4, and 64.5 g/100 g, respectively. The dry weight of cecal contents, cecal wall weight, the amount of short chain fatty acids in cecal contents, the amount of bile acids in small intestinal contents, and fecal excretion of neutral sterols increased logarithmically with increasing DF, while total plasma cholesterol concentration decreased. On the other hand, hepatic CYP7A1 activity, fecal dry weight, and fecal excretion of bile acids increased linearly with increasing DF, while body weight gain decreased. The hypocholesterolemic effect of HACS in OVX-rats appeared to be more effective by heat-moisture treatment.

Preparation of Tartary Buckwheat Protein Product and Its Improving Effect on Cholesterol Metabolism in Rats and Mice Fed Cholesterol‐Enriched Diet

Tartary buckwheat protein product (TBP) was prepared from buckwheat flour by alkali extraction and isoelectric precipitation. The protein content of TBP was 45.8%, and its amino acid composition of TBP was similar to that of common buckwheat protein product (BWP). SDS-PAGE analysis showed that the protein profile of TBP was partially different from that of BWP. TBP contained more quercetin (1710 mg/100 g) than BWP (5.4 mg/100 g), while there was a small difference in the contents of rutin between them. In experiment 1, the consumption of BWP and TBP at 20% net protein level for 13 d caused 32% and 25% reductions in serum cholesterol of rats fed cholesterol, respectively, when compared to the consumption of casein (P < 0.05). The reduction of serum cholesterol by BWP and TBP was associated with enhanced excretion of fecal neutral sterols. In experiment 2, the consumption of BWP and TBP for 27 d caused 62% and 43% reductions in the lithogenic index in mice fed cholesterol, respectively (P < 0.05). The reduction in lithogenic index was associated with enhanced excretion of fecal bile acids. Taken together, these results suggest a potential source of TBP as a functional food ingredient as well as BWP.

Insoluble Fraction of Buckwheat (Fagopyrum esculentum Moench) Protein Possessing Cholesterol-Binding Properties That Reduce Micelle Cholesterol Solubility and Uptake by Caco-2 Cells

Buckwheat (Fagopyrum esculentum Moench) protein (BWP) exhibits hypocholesterolemic activity in several animal models by increasing fecal excretion of neutral and acidic sterols. In the current study, the ability of BWP to disrupt micelle cholesterol solubility by sequestration of cholesterol was investigated. When BWP (0.2%) was incubated with cholesterol and micelle lipid components prior to micelle formation, cholesterol solubility was reduced 40%. In contrast, cholesterol solubility was not decreased when BWP (0.2%) was incubated after micelle formation and incorporation of soluble cholesterol. Buckwheat flour, from which BWP was derived, had no significant effect on cholesterol solubility. Cholesterol uptake in Caco-2 cells from micelles made in the presence of BWP (0.2%) was reduced by 47, 36, 35, and 33% when compared with buckwheat flour, bovine serum albumin, casein, and gelatin, respectively. Reduction in cholesterol uptake in Caco-2 cells was dose-dependent, with maximum reductions at 0.1-0.4% BWP. In cholesterol-binding experiments, 83% of the cholesterol was associated with an insoluble BWP fraction, indicating strong cholesterol-binding capacity that disrupts solubility and uptake by Caco-2 cells.

Direct Intestinal Cholesterol Secretion Contributes Significantly to Total Fecal Neutral Sterol Excretion in Mice

Hepatobiliary secretion is generally believed to be an integral step in the pathway of cholesterol excretion from the body. Here we have investigated the validity of this paradigm in mice. Cholesterol balance was assessed by measuring intake, excretion, and biliary output in different mouse models. Direct secretion of cholesterol from the luminal side of enterocytes was studied by perfusion of isolated segments of the small intestine in mice. Cholesterol input and output measurements in different mouse models revealed that fecal neutral sterol excretion was higher than the sum of dietary cholesterol intake and biliary cholesterol secretion indicating the existence of an alternative pathway. Here we show that substantial amounts of cholesterol can be secreted directly by enterocytes. Transintestinal cholesterol secretion is a specific process observed throughout the small intestine (proximal > medial > distal). Secretion depended on the presence of a cholesterol acceptor and was strongly stimulated by bile salts and phospholipids. The capacity of the pathway was sufficient to account for the missing cholesterol in the balance studies. The contribution of this pathway to cholesterol excretion in mice is approximately twice that of the biliary pathway. In mice, the intestine plays a significant role in removal of cholesterol from the body.

Some bovine proteins behave as dietary fibres and reduce serum lipids in rats

We examined the physiological importance of bovine dietary proteins in rats fed diets prepared from bovine Achilles' tendons and arteries. Rats were fed for 4 weeks, with a 20% casein diet (CON), in comparison with two diets containing 15% casein and 5% of either bovine Achilles' tendon (AC) or artery (AR) protein preparations. The serum total cholesterol concentration and non-HDL-cholesterol level in the AR-fed group were significantly lower (P< 0.05) than those in the CON-fed group at the end of the 4-week feeding period. The hepatic mRNA were measured, and the hydroxyl methyl glutaryl-CoA reductase mRNA level was significantly lower (P< 0.05) in the AR-fed group compared with the CON-fed group. Total hepatic cholesterol concentration in AC-fed rats was significantly (P < 0.05) higher than in the CON-fed group. The serum TAG concentration and fatty acid synthase mRNA level in AC- and AR-fed groups were significantly lower (P<0.05) compared with the CON-fed group throughout the feeding period. Faecal neutral sterol excretion was significantly (P<0.05) higher in the AC- and AR-fed groups compared with the CON-fed group. The results of the present study demonstrate that some bovine dietary proteins have similar functions as dietary fibres, lowering serum lipid concentration by enhancing faecal neutral sterol excretion or suppressing lipid synthesis in the liver. Moreover, favourable amino acid compositions in the AR and AC preparations may also have a lowering effect on plasma lipid concentration in bovine protein diet-fed groups.

The lipid-lowering effect of ezetimibe in pure vegetarians

Results of previous studies have shown that ezetimibe (10 mg/day) reduces LDL cholesterol in patients with mild hypercholesterolemia on a normal-cholesterol diet (dietary intake of 200-500 mg/day) by 16-22%. However, the LDL cholesterol-lowering effect of ezetimibe in subjects with an extremely low dietary cholesterol intake (vegetarians) has not been studied. We conducted a randomized, double-blind, placebo-controlled, two-phase crossover study in 18 healthy pure vegetarians to assess the effect of ezetimibe (10 mg/day) on plasma lipids, cholesterol absorption, and its synthesis. Treatment periods lasted 2 weeks each, with an intervening 2 week washout period. Fractional cholesterol absorption was determined using the continuous dual stable isotope feeding method. Mean dietary cholesterol intake in the pure vegetarians was extremely low and averaged 29.4 +/- 16.8 and 31.4 +/- 14.4 mg/day during the placebo and ezetimibe administration phases, respectively. Fractional cholesterol absorption during the placebo phase was 48.2 +/- 8.2% and was decreased by 58% during ezetimibe treatment to 20.2 +/- 6.2% (P < 0.001). This change in intestinal cholesterol absorption was followed by a significant reduction in LDL cholesterol of 17.3%. In individuals with extremely low dietary cholesterol intake, treatment with ezetimibe (10 mg/day) leads to a significant reduction of cholesterol absorption and a clinically relevant decrease of plasma LDL cholesterol, comparable to that of subjects with a normal dietary cholesterol intake. Thus, the lipid-lowering effect of ezetimibe is mediated mainly through a reduction of the absorption of endogenous (biliary) cholesterol.

A Rice Bran Oil Diet Increases LDL-Receptor and HMG-CoA Reductase mRNA Expressions and Insulin Sensitivity in Rats with Streptozotocin/Nicotinamide-Induced Type 2 Diabetes

A rice bran oil (RBO) diet can reduce plasma lipids; this was attributed to the specific components, gamma-oryzanol and gamma-tocotrienol, which individually were shown to be hypocholesterolemic; however, the mechanism of their effects on diabetic hyperlipidemia and the development of diabetes is not known. Rats with streptozotocin/nicotinamide-induced type 2 diabetes were divided into control, RO10, and RO15 groups, and fed cholesterol-free diets containing 0, 10, and 15 g RBO with 0, 352, and 528 g gamma-oryzanol and 0, 6.0 and 9.0 mg gamma-tocotrienol/100 g diet for 4 wk. Diabetic rats fed the RBO diet had greater insulin sensitivity (P = 0.02) than rats fed the control diet. Diabetic rats fed the RBO diet also had lower plasma triglyceride (P = 0.003), LDL cholesterol (P = 0.028), and hepatic triglyceride concentrations (P = 0.04), as well as greater fecal neutral sterol and bile acid excretion than those fed the control diet. After 4 wk, there was an approximately 100% (P < 0.001) increase in the abundance of hepatic cholesterol 7alpha-hydroxylase, an 89% (P < 0.001) increase in the hepatic LDL-receptor, and a 50% (P < 0.001) increase in hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA in rats fed the RBO diet compared with those fed the control diet. These findings support the conclusion that a rice bran oil-containing diet can significantly suppress hyperlipidemic and hyperinsulinemic responses in diabetic rats. The high contents of gamma-oryzanol and gamma-tocotrienol in RBO can lead to increased fecal neutral sterol and bile acid excretion, via upregulation of cholesterol synthesis and catabolism.

Structured triglycerides containing caprylic (8:0) and oleic (18:1) fatty acids reduce blood cholesterol concentrations and aortic cholesterol accumulation in hamsters

The effects of structured triglycerides containing one long chain fatty acid (oleic acid, C18:1) and one short chain saturated fatty acid (caprylic acid, 8:0) on lipidemia, liver and aortic cholesterol, and fecal neutral sterol excretion were investigated in male Golden Syrian hamsters fed a hypercholesterolemic regimen consisting of 89.9% commercial ration to which was added 10% coconut oil and 0.1% cholesterol (w/w). After 2 weeks on the HCD diet, the hamsters were bled, following an overnight fast (16 h) and placed into one of three dietary treatments of eight animals each based on similar plasma cholesterol levels. The hamsters either continued on the HCD diet or were placed on diets in which the coconut oil was replaced by one of two structured triglycerides, namely, 1(3),2-dicaproyl-3(1)-oleoylglycerol (OCC) or 1,3-dicaproyl-2-oleoylglycerol (COC) at 10% by weight. Plasma total cholesterol (TC) in hamsters fed the OCC and COC compared to the HCD were reduced 40% and 49%, respectively ( P < 0.05). Similarly, hamsters fed the OCC and COC diets reduced their plasma nonHDL cholesterol levels by 47% and 57%, respectively ( P < 0.05), compared to hamsters fed the HCD after 2 weeks of dietary treatment. Although hamsters fed the OCC (−26%) and COC (−32%) had significantly lower plasma HDL levels compared to HCD, ( P < 0.05), the plasma nonHDL/HDL cholesterol ratio was significantly lower ( P < 0.05) compared to the HCD for the OCC-fed (−27%) and the COC-fed (−38%) hamsters, respectively. Compared to the HCD group, aortic esterified cholesterol was 20% and 53% lower for the OCC and COC groups, respectively, with the latter reaching statistical significance, P < 0.05. In conclusion, the hamsters fed the structured triglyceride oils had lower blood cholesterol levels and lower aortic accumulation of cholesterol compared to the control fed hamsters.

Policosanol Has No Antioxidant Activity in Human Low-Density Lipoprotein but Increases Excretion of Bile Acids in Hamsters

Policosanol is a group of long chain primary alcohols and has been shown to reduce blood cholesterol levels and to inhibit the oxidation of low-density lipoprotein (LDL). The present study examined (i) the effect of policosanol supplementation in the diet on the fecal excretion of neutral and acidic sterols in hamsters and (ii) the antioxidant activity of policosanol in human LDL. Golden Syrian hamsters were divided into four groups (n = 12/each) fed one of the four diets containing 0 (control), 0.38, 0.75, and 1.50 g kg(-1) policosanol for 6 weeks. It was found that hamsters given 0.38-1.5 g kg(-1) diets had a serum total cholesterol level lowered by 15-25% and had a high-density lipoprotein cholesterol elevated by 7-16.8%. It was found that policosanol increased the excretion of acidic sterols by 25-73%. Contrary to that in previous reports, policosanol had no apparent anti-LDL oxidation activity when 1-tetracosanol, 1-hexacosanol, and 1-octacosanol were incubated in human LDL. Policosanol also possessed no scavenging activity on the free radical2,2-diphenyl-1-picrylhydrazyl. These data provide evidence that in addition to the effect of HMG-CoA reductase, the cholesterol-lowering activity of policosanol is partially mediated by its inhibition on the absorption of bile acids, but these data disprove the claim that policosanol is an antioxidant.