Plasma Lipoprotein Cholesterol Concentrations Research Articles

Sugar-Sweetened Beverage Consumption and Plasma Lipoprotein Cholesterol, Apolipoprotein, and Lipoprotein Particle Size Concentrations in US Adults

Prospective cohort studies have found a relation between sugar-sweetened beverage (SSB) consumption (sodas and fruit drinks) and dyslipidemia. There is limited evidence linking SSB consumption to emerging features of dyslipidemia, which can be characterized by variation in lipoprotein particle size, remnant-like particle (RLP), and apolipoprotein concentrations. To examine the association between SSB consumption and plasma lipoprotein cholesterol, apolipoprotein, and lipoprotein particle size concentrations among US adults. We examined participants from the Framingham Offspring Study (FOS; 1987-1995, n = 3047) and the Women's Health Study (1992, n = 26,218). Concentrations of plasma LDL cholesterol, apolipoprotein B (apoB), HDL cholesterol, apolipoprotein A1 (apoA1), triglyceride (TG), and non-HDL cholesterol, as well as total cholesterol:HDL cholesterol ratio and apoB:apoA1 ratio, were quantified in both cohorts; concentrations of apolipoprotein E, apolipoprotein C3, RLP-TG, and RLP cholesterol (RLP-C) were measured in the FOS only. Lipoprotein particle sizes were calculated from nuclear magnetic resonance signals for lipoprotein particle subclass concentrations (TG-rich lipoprotein particles [TRL-Ps]: very large, large, medium, small, and very small; LDL particles [LDL-Ps]: large, medium, and small; HDL particles [HDL-Ps]: large, medium, and small). SSB consumption was estimated from food frequency questionnaire data. We examined the associations between SSB consumption and all lipoprotein and apoprotein measures in linear regression models, adjusting for confounding factors such as lifestyle, diet, and traditional lipoprotein risk factors. SSB consumption was positively associated with LDL cholesterol, apoB, TG, RLP-TG, RLP-C, and non-HDL cholesterol concentrations and total cholesterol:HDL cholesterol and apoB:apoA1 ratios; and negatively associated with HDL cholesterol and apoA1 concentrations (P-trend range: <0.0001 to 0.008). After adjustment for traditional lipoprotein risk factors, SSB consumers had smaller LDL-P and HDL-P sizes; lower concentrations of large LDL-Ps and medium HDL-Ps; and higher concentrations of small LDL-Ps, small HDL-Ps, and large TRL-Ps (P-trend range: <0.0001 to 0.001). Higher SSB consumption was associated with multiple emerging features of dyslipidemia that have been linked to higher cardiometabolic risk in US adults.

Effects of increases in dietary fat intake on plasma lipid and lipoprotein cholesterol concentrations and associated enzyme activities in cats

To determine the effects of increases in dietary intake of polyunsaturated and saturated fatty acids on plasma lipid and lipoprotein concentrations and activity of associated enzymes in healthy domestic cats. 16 healthy adult sexually intact female cats. A baseline diet (40% energy from fat) and 4 test diets, with increased amounts of fat (51% and 66% energy from fat) from the addition of polyunsaturated and saturated fatty acids, were fed for 6 weeks each. Plasma cholesterol, triglyceride, and lipoprotein cholesterol concentrations, along with activities of lipoprotein lipase, hepatic lipase, and lecithin-cholesterol acyl transferase, were measured at the end of each feeding period. Diet, amount of fat, or ratio of polyunsaturated to saturated fatty acids had no effect on plasma concentrations of cholesterol, triglycerides, and very-low-density or high-density lipoproteins or the activity of lecithin-cholesterol acyl transferase. Low-density lipoprotein concentrations were significantly lower in cats fed a high-fat diet containing polyunsaturated fatty acids. Lipoprotein concentration and hepatic lipase activity were significantly higher in cats fed the fat-supplemented diets, and this was unrelated to whether diets were enriched with polyunsaturated or saturated fatty acids. Diets containing up to 66% of energy from fat were tolerated well by healthy cats and did not affect plasma lipid concentrations. Therefore, high-fat diets probably will not contribute to hypercholesterolemia or hypertriglyceridemia in cats.

High-Density Lipoprotein Cholesterol Efflux, Nitration of Apolipoprotein A-I, and Endothelial Function in Obese Women

Subjects at risk of atherosclerosis might have dysfunctional high-density lipoprotein (HDL) despite normal cholesterol content in the plasma. We considered whether the efflux of excess cellular cholesterol to HDL from obese subjects is associated with impaired arterial endothelial function, a biomarker of cardiovascular risk. A total of 54 overweight (body mass index [BMI] 25 to 29.9 kg/m(2)) or obese (BMI ≥30 kg/m(2)) women, aged 46 ± 11 years, were enrolled in a worksite wellness program. The HDL cholesterol averaged 57 ± 17 mg/dl and was inversely associated with the BMI (r = -0.419, p = 0.002). Endothelial function was assessed using brachial artery flow-mediated dilation. Cholesterol efflux from (3)H-cholesterol-labeled baby hamster kidney cells transfected with the adenosine triphosphate-binding cassette transporter 1 showed 8.2% to 22.5% cholesterol efflux within 18 hours when incubated with 1% serum and was positively correlated with brachial artery flow-mediated dilation (p <0.05), especially in the 34 subjects with BMI ≥30 kg/m(2) (r = 0.482, p = 0.004). This relation was independent of age, HDL or low-density lipoprotein cholesterol concentrations in plasma, blood pressure, or insulin resistance on stepwise multiple regression analysis (β = 0.31, R(2) = 0.21, p = 0.007). Nitration of apolipoprotein A-I tyrosine residues (using sandwich enzyme-linked immunosorbent assay) was significantly greater in women with a BMI ≥30 kg/m(2) and the lowest cholesterol efflux than in women with a BMI of 25 to 29.9 kg/m(2) and the greatest cholesterol efflux (p = 0.01). In conclusion, we have shown that decreased cholesterol efflux by way of the adenosine triphosphate-binding cassette transporter 1 is associated with increased nitration of apolipoprotein A-I in HDL and is an independent predictor of impaired endothelial function in women with a BMI of ≥30 kg/m(2). This finding suggests that the functional measures of HDL might be better markers for cardiovascular risk than the HDL cholesterol levels in this population.

Dietary polyunsaturated fatty acids may increase plasma LDL-cholesterol and plasma cholesterol concentrations in carriers of an ABCG1 gene single nucleotide polymorphism: Study in two Spanish populations

BackgroundABCG1 mediates cellular cholesterol transport, but there is very little known about the influence of ABCG1 polymorphisms on human plasma lipoprotein cholesterol concentrations or on the interactions of these polymorphisms with diet. ObjectiveOur objective was to investigate whether interactions between PUFA intake and ABCG1 polymorphisms modulate associations with plasma total cholesterol (TC), LDL- and HDL-cholesterol in two Spanish populations. MethodsWe grounded our investigation on two general population-based studies: the Hortega study (population A) and the Pizarra study (population B). Participants included 1178 individuals (50.0% women, age range 21–85 years) and 763 individuals (66% women, age range 23–73 years) from populations A and B, respectively, without lipid lowering drugs. Subjects were genotyped for ABCG1 variants. Biochemical measurements were taken by standard procedures. Dietary intakes were estimated with a validated questionnaire. ResultsIn population A, the A allele homozygotes of SNP rs4148102 had higher TC and LDLc concentrations in subjects on a high PUFA diet than did the carriers of the G allele (242.1±38.9 vs. 198.0±36.0mg/dL, p=0.003, and 149.8±37.9 vs. 111.4±32.1mg/dL, p=0.005, respectively), and significant gene–diet interactions were observed (p=0.020 and p=0.013, respectively). In population B, similar differences in TC and LDLc concentrations were also found in association with this SNP under a high PUFA diet (253.2±24.9 vs. 197.7±39.9mg/dL, p=0.009, and 171.8±20.5 vs. 120.4±34.2mg/dL, p=0.004, respectively), but the gene–diet interactions observed were not significant (p=0.379 and p=0.422, respectively). In the pooled populations, differences in the TC and LDLc concentrations increased (246.8±32.9 vs. 198.0±37.5, p=6×10−5, and 159.0±32.6 vs. 114.3±33.1, p=3×10−5, respectively), and significant gene–diet interactions were maintained (p=0.006 and p=0.003, respectively). ConclusionIn two Spanish populations, the ABCG1 polymorphism rs4148102 was associated with variations in plasma lipoprotein cholesterol concentrations in subjects with high PUFA intakes. Carriers of the AA genotype consuming high PUFA diet showed higher plasma LDLc concentrations.

582 PERSONAL ANXIETY AND RISK DEVELOPMENT OF CARDIOVASCULAR DISEASES AT POPULATION MEN 25-64 YEAR OLD DURING 24 YEARS (WHO “MONICA”)

Background: The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism.Aim: To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia.Design: A randomized double-blind sequential cross-over study.Subjects and methods: Thirty subjects of both genders (20 M/10 F), mean age 45.5±9.9 years (M±SD), BMI 26.6±2.2 kg/m2, with plasma cholesterol >5.17 and <7.76 mmol/l and plasma triglycerides <3.45 mmol/l, participated in the study. The study was performed after a wash-out period of 1 month and a run-in period of 1 month to stabilize patients on a standard diet (CHO 50%, fat 30%, protein 20%, fibre 20 g/day) plus placebo (maltodextrine plus aspartame 15 g/day). At the end of run-in, subjects were randomly assigned to receive sc-FOS (Actilight(R)) (10.6 g/day) or placebo (maltodextrine plus aspartame 15 g/day) with tea and/or coffee for a duration of 2 months and thereafter switched to the other treatment for additional 2 months. Plasma glucose, total and lipoprotein (VLDL, LDL, HDL) cholesterol and triglyceride concentrations were measured in the fasting state at the end of run-in and of each treatment period. At the end of the two treatment periods, patients consumed a standard test meal (protein 15%, carbohydrate 34%, fat 51%, kJ 3988) 1 h after the administration of 5.3 g of sc-FOS or placebo; plasma glucose, insulin, free fatty acid (FFA) and triglyceride responses to the test meal were evaluated.Results: No significant difference in fasting parameters was detected between the two treatments. After sc-FOS and placebo plasma cholesterol levels were, respectively, 6.47±0.70 and 6.44±0.78 mmol/l (n.s.) and plasma triglycerides were 1.53±0.71 and 1.56±0.53 mmol/l (n.s.). No significant differences were observed in cholesterol and triglyceride content of VLDL, LDL and HDL and in plasma Apo A1 levels; conversely, fasting plasma Lp(a) concentrations were significantly increased after sc-FOS (37±38 vs. 33±35 mg/dl; P<0.005). Postprandial responses of glucose, FFA and triglycerides were not significantly different between sc-FOS and placebo, while postprandial insulin response (incremental area) was significantly reduced after sc-FOS compared to placebo (14 490±7416 vs. 17 760±7710 pmol/l × 300 min; P<0.02).Conclusions: A moderate intake of sc-FOS has no major effects on lipid metabolism, both in the fasting and in the postprandial period, in individuals with mild hypercholesterolaemia. A small but significant increase of Lp(a) concentrations was observed with sc-FOS consumption together with a reduction of the postprandial insulin response; however, the clinical relevance of these small effects is unclear.

Comparison of measurement uncertainties in direct plasma low-density lipoprotein cholesterol method of measurement and indirect estimation according to Friedewald equation

Concentration of low-density lipoprotein (LDL) cholesterol in plasma is appropriate to detect coronary heart disease risk. Many laboratories use the Friedewald equation for estimating this quantity instead of direct measurement. Nine clinical laboratories having an Hitachi selected 10 adult patients having results of cholesterol, high-density lipoprotein (HDL) cholesterol, LDL-cholesterol, and triglyceride concentrations in serum or plasma. Additionally, LDL-cholesterol concentrations were estimated using the Friedewald equation. Combined and expanded uncertainties were calculated for all results. The mean relative combined uncertainty corresponding to direct measurement of LDL-cholesterol concentrations is 6.9% and that corresponding to estimation is 19.4%. The expanded uncertainty (k = 2) of a result equal to 3.40 mmol/L (the discriminant value universally used to detect cardiovascular risk) obtained by direct measurement and by estimation using the Friedewald equation, are 0.22 and 0.55 mmol/L, respectively. The uncertainty of the direct measurement is very much lower than the estimation with the Friedewald equation.

Effect of ezetimibe on plasma cholesterol levels, cholesterol absorption, and secretion of biliary cholesterol in laboratory opossums with high and low responses to dietary cholesterol

Partially inbred lines of laboratory opossums differ in plasma low-density lipoprotein cholesterol concentration and cholesterol absorption on a high-cholesterol diet. The aim of the present studies was to determine whether ezetimibe inhibits cholesterol absorption and eliminates the differences in plasma cholesterol and hepatic cholesterol metabolism between high and low responders on a high-cholesterol diet. Initially, we determined that the optimum dose of ezetimibe was 5 mg/(kg d) and treated 6 high- and 6 low-responding opossums with this dose (with equal numbers of controls) for 3 weeks while the opossums consumed a high-cholesterol and low-fat diet. Plasma and low-density lipoprotein cholesterol concentrations decreased significantly ( P < .05) in treated but not in untreated high-responding opossums. Plasma cholesterol concentrations increased slightly ( P < .05) in untreated low responders but not in treated low responders. The percentage of cholesterol absorption was significantly higher in untreated high responders than in other groups. Livers from high responders with or without treatment were significantly ( P < .01) heavier than livers from low responders with or without treatment. Hepatic cholesterol concentrations in untreated high responders were significantly ( P < .05) higher than those in low responders with or without treatment ( P < .001). The gall bladder bile cholesterol concentrations in untreated high responders were significantly ( P < .05) lower than those in other groups. A decrease in biliary cholesterol in low responders treated with ezetimibe was associated with a decrease in hepatic expression of ABCG5 and ABCG8. These studies suggest that ezetimibe decreases plasma cholesterol levels in high responders mainly by decreasing cholesterol absorption and increasing biliary cholesterol concentrations. Because ezetimibe's target is NPC1L1 and NPC1L1 is expressed in the intestine of opossums, its effect on cholesterol absorption may be mediated by inhibiting NPC1L1 function in the intestine.

Soy protein without isoflavones reduces aortic total and cholesterol ester concentrations greater than soy protein with isoflavones compared with casein in hypercholesterolemic hamsters

Abstract The present study was designed to investigate the effects of replacing casein with soy protein either containing isoflavones or not on plasma lipids and lipoprotein cholesterol concentrations and early aortic atherosclerosis (measured as aortic cholesterol concentration) in hypercholesterolemic hamsters. Thirty, 8-week-old, male F 1 B Golden Syrian hamsters were individually housed and fed a semipurified hypercholesterolemic diet (HCD) containing 22% casein, 20% coconut oil, 2% corn oil, and 0.12% cholesterol (wt/wt) for a period of 2 weeks. The hamsters were then divided into 3 groups of 10 based on similar mean fasting plasma cholesterol concentrations and placed on experimental diets for 6 weeks. Group 1 continued on the HCD (casein). Group 2 was fed the HCD with 22% water-washed soybean protein isolate (soy + I) (1.76 mg of isoflavones per gram of protein) in place of casein. Group 3 was fed the HCD with 22% alcohol-washed soybean protein isolate (soy − I) (0.08 mg isoflavones per gram of protein) in place of casein. Compared with hamsters fed casein, hamsters fed both soy diets had significant decreases in their plasma total and non–high-density lipoprotein (very low and low-density lipoprotein)–cholesterol concentrations by week 2, which continued across weeks 4 and 6. However, the hamsters fed the soy − I diet accumulated significantly less aortic total cholesterol compared with the hamsters fed casein and the soy + I diet. In addition, the hamsters fed the soy − I diet accumulated significantly less aortic cholesterol ester compared with the hamsters fed casein only. In conclusion, dietary replacement of casein with soy protein either containing isoflavones or not in hypercholesterolemic hamsters lowers plasma total and non–high-density lipoprotein–cholesterol concentrations; however, only the soy protein without isoflavones reduced aortic cholesterol accumulation.

Soy protein concentrate lowers serum high-density lipoprotein cholesterol concentrations compared with casein in ovariectomized rats fed a low-fat, cholesterol-free diet

Abstract The cholesterol-lowering properties of soy protein are commonly attributed to the presence of isoflavones in the product and hypercholesterolemia. The present study was designed to investigate the effects of either replacing casein with soy protein concentrate containing isoflavones or adding purified soy isoflavones to casein on plasma lipids and lipoprotein cholesterol concentrations in ovariectomized (OVX) rats fed a low-fat, cholesterol-free diet. Thirty-two female rats, 8 weeks of age, were fed 1 of 4 semipurified diets containing 21% protein by energy for 8 weeks. Group 1 was fed casein and was sham operated (CAS-S). Group 2 was fed casein and was OVX (CAS-O). Group 3 was fed soy protein concentrate containing isoflavones and was OVX (SPC-O). Group 4 was fed casein + soy isoflavones and was OVX (CAS-I-O). After 8 weeks of dietary treatment, the SPC-O rats had significantly lower serum total cholesterol (TC) concentrations compared with the CAS-S, CAS-O, and CAS-I-O rats. Furthermore, the SPC-O rats had significantly lower serum high-density lipoprotein–cholesterol (HDL-C) concentrations compared with the CAS-S, CAS-O, and CAS-I-O rats. The serum TC/HDL-C and non–HDL-C/HDL-C ratios were significantly increased in the SPC-O rats compared with those in the CAS-S and CAS-I-O rats. The primary conclusion of the present study is that dietary replacement of casein with soy protein concentrate containing isoflavones in OVX rats fed a low-fat, cholesterol-free diet significantly lowers the serum HDL-C concentration and raises the serum TC/HDL-C ratio greater than OVX alone, thereby possibly increasing the risk of developing atherosclerosis.

Effects of Dehulled Adlay on Plasma Glucose and Lipid Concentrations in Streptozotocin-induced Diabetic Rats fed a Diet Enriched in Cholesterol

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) is a cereal food for humans and has been also used as a superior medical herb substance and functional food for traditional treatment of diabetes in China. However, its scientific basis as a functional food is still unclear. The purpose of this study was to investigate the effect of dietary dehulled adlay on plasma lipid and glucose concentrations in diabetic rats. The diabetic male Sprague-Dawley (SD) rats, induced by injection of streptozotocin (60 mg/kg subcutaneously), were fed a cholesterol-rich diet (0.5% cholesterol) containing corn starch or dehulled adlay for four weeks. After completion of the experimental period, the abdominal adipose tissue and liver of rats were excised and weighed, and the plasma glucose, triglyceride, and lipoprotein cholesterol concentrations were assayed. The results showed that diabetic rats fed a dehulled adlay diet exhibited a greater adipose tissue weight (9.36 +/- 3.43 vs. 5.39 +/- 3.04 g, p < 0.05) and a reduced food intake (39.3 +/- 5.9 vs. 61.0 +/- 11.7 g/day, p < 0.05) when compared with animals fed a cornstarch diet. Significantly decreased plasma glucose (261.6 +/- 96.6 vs. 422.1 +/- 125.4 mg/dL, p < 0.05), total cholesterol (289.4 +/- 140.6 vs. 627.3 +/- 230.5 mg/dL, p < 0.05), and triglyceride (52.3 +/- 14.4 vs. 96.5 +/- 36.6 mg/dL, p < 0.05) levels were observed in rats fed the dehulled adlay diet. In addition, the ingestion of dehulled adlay appears to significantly decrease plasma low-density lipoprotein (LDL) plus very low-density lipoprotein (VLDL) cholesterol concentrations. Rats fed a dehulled adlay diet showed an increase in fecal weight and cholesterol contents of stools. Although a significantly decreased plasma thiobarbituric reactive substances (TBARS) value was observed in diabetic rats fed the dehulled adlay diet (6.2 +/- 3.4 vs. 11.0 +/- 3.8 nmol malondialdehyde (MDA)/mL, p < 0.05), no significant difference in the hepatic TBARS value was observed between the two dietary groups. Results from the present study suggest that dehulled adlay exhibited not only a hypolipidemic effect but also displayed a hypoglycemic ability in diabetic rats, indicating that dehulled adlay may play an important role in the regulation of plasma lipid and glucose metabolisms in diabetic rats induced by streptozotocin.

The Form of Dietary Conjugated Linoleic Acid Does Not Influence Plasma and Liver Triacylglycerol Concentrations in Syrian Golden Hamsters

Several studies have shown that conjugated linoleic acid (CLA) supplementation can improve the plasma lipid profile and thereby probably decrease the risk for development of atherosclerosis. The aim of the present study was to compare the effects on plasma and organ lipids of different dietary forms of CLA: triacylglycerol (TAG), diacylglycerol (DAG), monoacylglycerol (MAG), and fatty acid ethyl esters (FAEEs). DAG-, MAG-, and FAEE-CLA were produced by enzymatic interesterifications and all supplements were composed of a 1:1 mixture of the 2 major CLA isomers: cis-9, trans-11 and trans-10, cis-12. Male Syrian Golden hamsters were fed mildly atherogenic diets (10 g butter/100 g, 0.1 g cholesterol/100 g) supplemented with 0.5 g CLA/100 g or without CLA (control) for 8 wk. Liver weights were greater in the TAG- and FAEE-CLA groups than in the control group. In general, the form of CLA did not differentially affect plasma or liver cholesterol or plasma lipoprotein cholesterol concentrations, but only the TAG-CLA group had a higher final plasma TAG concentration than the control group. Both CLA isomers were incorporated into plasma, livers, and spleens. The results of the present study suggest that the form in which CLA is supplemented in the diet does not affect hamster plasma and liver TAG concentrations. The TAG-CLA form, a frequently used form of supplemental CLA, increases plasma TAG concentrations. If similar effects occur in humans, supplemental TAG-CLA cannot be considered to be beneficial given the relation between plasma TAG and the development of atherosclerosis.

Rice bran oil and oryzanol reduce plasma lipid and lipoprotein cholesterol concentrations and aortic cholesterol ester accumulation to a greater extent than ferulic acid in hypercholesterolemic hamsters

Our laboratory has reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Because RBO has a greater content of the unsaponifiables, which also lower cholesterol compared to most vegetable oils, we wanted to know whether oryzanol or ferulic acid, two major unsaponifiables in RBO, has a greater cholesterol-lowering activity. Forty-eight F 1B Golden Syrian hamsters ( Mesocricetus auratus) (BioBreeders, Watertown, MA) were group housed (three per cage) in cages with bedding in an air-conditioned facility maintained on a 12-h light/dark cycle. The hamsters were fed a chow-based hypercholesterolemic diet (HCD) containing 10% coconut oil and 0.1% cholesterol for 2 weeks, at which time they were bled after an overnight fast (16 h) and segregated into 4 groups of 12 with similar plasma cholesterol concentrations. Group 1 (control) continued on the HCD, group 2 was fed the HCD containing 10% RBO in place of coconut oil, group 3 was fed the HCD plus 0.5% ferulic acid and group 4 was fed the HCD plus 0.5% oryzanol for an additional 10 weeks. After 10 weeks on the diets, plasma total cholesterol (TC) and non-high-density lipoprotein cholesterol (HDL-C) (very low- and low-density lipoprotein) concentrations were significantly lower in the RBO (−64% and −70%, respectively), the ferulic acid (−22% and −24%, respectively) and the oryzanol (−70% and −77%, respectively) diets compared to control. Plasma TC and non-HDL-C concentrations were also significantly lower in the RBO (−53% and −61%, respectively) and oryzanol (−61% and −70%, respectively) diets compared to the ferulic acid. Compared to control and ferulic acid, plasma HDL-C concentrations were significantly higher in the RBO (10% and 20%, respectively) and oryzanol (13% and 24%, respectively) diets. The ferulic acid diet had significantly lower plasma HDL-C concentrations compared to the control (−9%). The RBO and oryzanol diets were significantly lower for plasma triglyceride concentrations compared to the control (−53% and −65%, respectively) and ferulic acid (−47% and −60%, respectively) diets. Hamsters fed the control and ferulic acid diets had significantly higher plasma vitamin E concentrations compared to the RBO (201% and 161%, respectively) and oryzanol (548% and 462%, respectively) diets; the ferulic acid and oryzanol diets had significantly lower plasma lipid hydroperoxide levels than the control (−57% and −46%, respectively) diet. The oryzanol-fed hamsters excreted significantly more coprostenol and cholesterol in their feces than the ferulic acid (127% and 120%, respectively) diet. The control diet had significantly greater aortic TC and FC accumulation compared to the RBO (115% and 89%, respectively), ferulic acid (48% and 58%, respectively) and the oryzanol (74% and 70%, respectively) diets. However, only the RBO and oryzanol diets had significantly lower aortic cholesterol ester accumulation compared to the control (−73% and −46%, respectively) diet. The present study suggests that at equal dietary levels, oryzanol has a greater effect on lowering plasma non-HDL-C levels and raising plasma HDL-C than ferulic acid, possibly through a greater extent to increase fecal excretion of cholesterol and its metabolites. However, ferulic acid may have a greater antioxidant capacity via its ability to maintain serum vitamin E levels compared to RBO and oryzanol. Thus, both oryzanol and ferulic acid may exert similar antiatherogenic properties, but through different mechanisms.

Conjugated linoleic acid isomers reduce blood cholesterol levels but not aortic cholesterol accumulation in hypercholesterolemic hamsters

The aim of the present study was to characterize plasma lipids and lipoprotein cholesterol and glucose concentrations in hamsters fed either cis-9,trans-11 CLA (9c,11 tCLA); trans-10,cis-12 CLA (10t,12c CLA); or linoleic acid (LA) on the accumulation of aortic cholesterol in hypercholesterolemic hamsters. One hundred male F1B strain Syrian Golden Hamsters (Mesocricetus auratus) (BioBreeders Inc., Watertown, MA) approximately 9 wk of age were housed in individual stainless steel hanging cages at room temperature with a 12-h light/dark cycle. Hamsters were given food and water ad libitum. Following a 1-wk period of acclimation, the hamsters were fed a chow-based (nonpurified) hypercholesterolemic diet (HCD) containing 10% coconut oil (92% saturated fat) and 0.1% cholesterol for 2 wk. After an overnight fast, the hamsters were bled and plasma cholesterol concentrations were measured. The hamsters were then divided into 4 groups of 25 based on similar mean plasma VLDL and LDL cholesterol (nonHDL-C) concentrations. Group 1 remained on the HCD (control). Group 2 was fed the HCD plus 0.5% 9c,11t CLA isomer. Group 3 was fed the HCD plus 0.5% 10t,12c CLA isomer. Group 4 was fed the HCD plus 0.5% LA. Compared with the control, both CLA isomers and LA had significantly lower plasma total cholesterol and HDL cholesterol concentrations (P < 0.001) after 12 but not 8 wk of treatment and were not significantly different from each other. Also, both CLA isomers had significantly lower plasma nonHDL-C concentrations (P < 0.01) compared with the control after 12 but not 8 wk of treatment and were not significantly different from each other or the LA-fed hamsters. Plasma TG concentrations were significantly higher (P < 0.004) with the 10t, 12c CLA isomer compared with the other treatments at 8 but not at 12 wk of treatment. Plasma TG concentrations were also significantly lower (P < 0.03) with the 9c,11t CLA isomer compared with the control at 12 wk of treatment. Also, the 10t,12c CLA isomer and LA had significantly higher plasma glucose concentrations compared with the control and 9c,11t CLA isomer (P < 0.008) at 12 wk of treatment, whereas at 8 wk, only the LA treatment had significantly higher plasma glucose concentrations (P < 0.001) compared with the 9c,11t CLA isomer. Although liver weights were significantly higher in 10t,12c CLA isomer-fed hamsters, liver total cholesterol, free cholesterol, cholesterol ester, and TG concentrations were significantly lower in these hamsters compared with hamsters fed the control, 9c,11t CLA isomer, and LA diets (P< 0.05). The 9c,11t CLA isomer and LA diets tended to reduce cholesterol accumulation in the aortic arch, whereas the 10t,12c CLA isomer diet tended to raise cholesterol accumulation compared with the control diet; however, neither was significant. In summary, no differences were observed between the CLA isomers for changes in plasma lipids or lipoprotein cholesterol concentrations. However, the 9c,11t CLA isomer did appear to lower plasma TG and glucose concentrations compared with the 10t,12c CLA isomer. Such differences may increase the risk of insulin resistance and type 2 diabetes in humans when the 10t,12c CLA isomer is fed separately.

Adult sterol metabolism is not affected by a positive sterol balance in the neonatal Golden Syrian hamster

Dietary components impact metabolism early in life. Some of the diet-induced effects are long lasting and can lead to various adult-based diseases. In the current studies, we examined the short-term effects of dietary cholesterol on neonatal hepatic sterol metabolism and the long-term effects that those early-life diets had on sterol metabolism in adulthood. Neonatal hamsters began consuming solid food as a supplement to milk by 5 days of age; diets contained 0 or 2% added cholesterol (wt/wt). By 10 days of age, plasma and liver cholesterol concentrations were 3.2- and 2.5-fold greater, respectively, in the neonates fed cholesterol. Hepatic sterol synthesis rates were suppressed 65% in cholesterol-fed neonates compared with control neonates. By 20 days of age, plasma and liver cholesterol concentrations were still greater and sterol synthesis rates were now suppressed maximally in neonates fed cholesterol compared with control neonates. The expression level of an apolipoprotein B-containing lipoprotein receptor (low-density lipoprotein receptor-related protein) was greater and the mature form of the sterol regulatory element-binding protein-2 was similar in livers of 20-day-old control neonates compared with control neonates at 10 days of age. To test whether the change in sterol balance in the neonatal period had a lasting effect on hepatic sterol metabolism, all animals were weaned on a low-cholesterol diet. At 70 days of age, hepatic sterol synthesis rates, plasma lipoprotein and liver cholesterol concentrations, and bile acid pool sizes and compositions were measured. Sterol balance in the adults was similar between animals fed either diet early in life, as demonstrated by a lack of difference in any parameter measured. Thus, even though dietary cholesterol suppressed hepatic sterol synthesis rates dramatically in the neonatal hamster, the change has little impact on sterol balance later in life.

Plant sterols and endurance training combine to favorably alter plasma lipid profiles in previously sedentary hypercholesterolemic adults after 8 wk

Plant sterol supplementation was shown to reduce total and LDL-cholesterol concentrations, whereas endurance training was shown to increase HDL-cholesterol concentrations and decrease triacylglycerol concentrations. The objective was to examine the effect of plant sterols, endurance training, and the combination of plant sterols and endurance training on plasma lipid and lipoprotein cholesterol concentrations, sterol concentrations, and cholesterol precursor concentrations in previously sedentary hypercholesterolemic adults. In an 8-wk, placebo-controlled, parallel-arm clinical trial, 84 subjects were randomly assigned to receive 1 of 4 interventions: 1) combination of sterols and exercise, 2) exercise, 3) sterols, or 4) control treatment. Sterol supplementation significantly (P < 0.01) decreased total cholesterol concentrations by 8.2% from baseline. In addition, sterols significantly (P < 0.01) lowered absolute LDL-cholesterol concentrations after treatment but had no effect on the percentage change from the beginning to the end of the trial. Exercise significantly (P < 0.01) increased HDL-cholesterol concentrations by 7.5% and decreased triacylglycerol concentrations by 13.3% from baseline. Moreover, sterol supplementation significantly (P < 0.05) increased lathosterol, campesterol, and beta-sitosterol concentrations after treatment. Exercise significantly (P < 0.01) decreased percentage of body fat by 3.9% from the beginning to the end of the trial. In comparison with plant sterols or exercise alone, the combination of plant sterols and exercise yields the most beneficial alterations in lipid profiles. Implementation of such a combination therapy could improve lipid profiles in those at risk of coronary artery disease.

Effect of dietary cholesterol with or without saturated fat on plasma lipoprotein cholesterol levels in the laboratory opossum (Monodelphis domestica) model for diet-induced hyperlipidaemia.

Laboratory opossums (Monodelphis domestica) show extreme genetic variability in their responsiveness to dietary lipids; a great proportion of the genetic variability in responsiveness is due to a single major gene. To determine whether the major gene for dietary response detected by genetic analysis in opossums is responsive to dietary cholesterol or dietary saturated fat, or a combination of both, we used males and females of susceptible and resistant lines of laboratory opossums that were 5 to 7 months old. The animals were challenged with three different experimental diets (high-cholesterol diets with or without high saturated fat from lard or coconut oil) and plasma lipoproteins were measured. Plasma and VLDL+LDL-cholesterol concentrations increased several-fold when the animals were fed the diet containing elevated cholesterol (P<0.001) or elevated cholesterol and fat (P<0.001) and differed between the two lines when they were fed high-cholesterol diets with or without fat (P<0.001). Plasma HDL-cholesterol concentrations were higher (P<0.05) in animals of the resistant line than in the susceptible line when they were fed the basal diet (550 (SEM 30) v. 440 (SEM 20) mg/l) and when they were fed the low-cholesterol and high-fat diet (600 (SEM 30) v. 490 (SEM 30) mg/l). Dietary coconut oil and lard had similar effects on plasma lipoprotein cholesterol concentrations in the susceptible line of opossums. A reduction in dietary cholesterol by 50 % with either the lard or coconut oil blunted the plasma cholesterol response. The results from the present studies suggest that the major gene for dietary response previously detected by genetic analysis in laboratory opossums affects the response to dietary cholesterol but not to saturated fat.

Effects of short-chain fructo-oligosaccharides on glucose and lipid metabolism in mild hypercholesterolaemic individuals

Background: The intake of 10g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism. Aim: To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia. Design: A randomized double-blind sequential cross-over study. Subjects and methods: Thirty subjects of both genders (20M/10F), mean age 45.5±9.9years (M±SD), BMI 26.6±2.2kg/m2, with plasma cholesterol >5.17 and <7.76mmol/l and plasma triglycerides <3.45mmol/l, participated in the study. The study was performed after a wash-out period of 1 month and a run-in period of 1 month to stabilize patients on a standard diet (CHO 50%, fat 30%, protein 20%, fibre 20g/day) plus placebo (maltodextrine plus aspartame 15g/day). At the end of run-in, subjects were randomly assigned to receive sc-FOS (Actilight(R)) (10.6g/day) or placebo (maltodextrine plus aspartame 15g/day) with tea and/or coffee for a duration of 2 months and thereafter switched to the other treatment for additional 2 months. Plasma glucose, total and lipoprotein (VLDL, LDL, HDL) cholesterol and triglyceride concentrations were measured in the fasting state at the end of run-in and of each treatment period. At the end of the two treatment periods, patients consumed a standard test meal (protein 15%, carbohydrate 34%, fat 51%, kJ 3988) 1h after the administration of 5.3g of sc-FOS or placebo; plasma glucose, insulin, free fatty acid (FFA) and triglyceride responses to the test meal were evaluated. Results: No significant difference in fasting parameters was detected between the two treatments. After sc-FOS and placebo plasma cholesterol levels were, respectively, 6.47±0.70 and 6.44±0.78mmol/l (n.s.) and plasma triglycerides were 1.53±0.71 and 1.56±0.53mmol/l (n.s.). No significant differences were observed in cholesterol and triglyceride content of VLDL, LDL and HDL and in plasma Apo A1 levels; conversely, fasting plasma Lp(a) concentrations were significantly increased after sc-FOS (37±38 vs. 33±35mg/dl; P<0.005). Postprandial responses of glucose, FFA and triglycerides were not significantly different between sc-FOS and placebo, while postprandial insulin response (incremental area) was significantly reduced after sc-FOS compared to placebo (14490±7416 vs. 17760±7710pmol/l × 300min; P<0.02). Conclusions: A moderate intake of sc-FOS has no major effects on lipid metabolism, both in the fasting and in the postprandial period, in individuals with mild hypercholesterolaemia. A small but significant increase of Lp(a) concentrations was observed with sc-FOS consumption together with a reduction of the postprandial insulin response; however, the clinical relevance of these small effects is unclear.

Dietary Soy β-Conglycinin (7S Globulin) Inhibits Atherosclerosis in Mice

Although beta-conglycinin (7S globulin), a major soy storage protein, stimulates the expression of LDL receptors and the degradation of LDL by hepatocytes in vitro, the in vivo effects of dietary beta-conglycinin on the cardiovascular system are unknown. We assessed the effects of dietary beta-conglycinin and other soy peptide fractions on the development of atherosclerosis in atherosclerosis-susceptible mice. At 6 wk of age, male and ovariectomized female apolipoprotein (apo) E-null mice and LDL receptor-null, apoB transgenic mice were assigned randomly to treatment groups that differed only in the source of dietary protein: 1) casein/lactalbumin, 2) isoflavone-containing soy protein isolate, 3) beta-conglycinin, 4) glycinin (11S globulin, another major soy storage protein), 5) beta-conglycinin-devoid soy protein, and 6) W008 (a peptide fraction produced by hydrolysis and precipitation of soy protein isolate). After 4 mo, aortic atherosclerosis (cholesteryl ester content) and plasma lipoprotein cholesterol concentrations were quantified using GLC. Relative to mice fed casein/lactalbumin-based diets, the extent of atherosclerosis was reduced in ovariectomized female mice fed all soy protein-containing diets. Relative to mice fed isoflavone-containing soy protein isolate, atherosclerosis was reduced only in mice fed the beta-conglycinin-containing diet. Mean reductions were 39 and 67% (all P <0.05) in male and ovariectomized female apoE null mice and 66% (P < 0.05) in male LDL receptor null mice. These effects were unrelated to variation in isoflavone content of the protein source and only minimally related to plasma lipoprotein cholesterol concentrations. We conclude that a diet rich in beta-conglycinin has atheroprotective effects that greatly exceed those of isoflavone-containing soy protein isolate and do not depend on LDL receptors or influences on plasma lipoproteins.

Identification of ACAT1- and ACAT2-specific inhibitors using a novel, cell-based fluorescence assay: individual ACAT uniqueness

Acyl CoA:cholesterol acyltransferase 1 (ACAT1) and ACAT2 are enzymes responsible for the formation of cholesteryl esters in tissues. While both ACAT1 and ACAT2 are present in the liver and intestine, the cells containing either enzyme within these tissues are distinct, suggesting that ACAT1 and ACAT2 have separate functions. In this study, NBD-cholesterol was used to screen for specific inhibitors of ACAT1 and ACAT2. Incubation of AC29 cells, which do not contain ACAT activity, with NBD-cholesterol showed weak fluorescence when the compound was localized in the membrane. When AC29 cells stably transfected with either ACAT1 or ACAT2 were incubated with NBD-cholesterol, the fluorescent signal localized to the nonpolar core of cytoplasmic lipid droplets was strongly fluorescent and was correlated with two independent measures of ACAT activity. Several compounds were found to have greater inhibitory activity toward ACAT1 than ACAT2, and one compound was identified that specifically inhibits ACAT2. The demonstration of selective inhibition of ACAT1 and ACAT2 provides evidence for uniqueness in structure and function of these two enzymes. To the extent that ACAT2 is confined to hepatocytes and enterocytes, the only two cell types that secrete lipoproteins, selective inhibition of ACAT2 may prove to be most beneficial in the reduction of plasma lipoprotein cholesterol concentrations.

Effects of short-chain fructo-oligosaccharides on glucose and lipid metabolism in mild hypercholesterolaemic individuals

Background: The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism. Aim: To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia. Design: A randomized double-blind sequential cross-over study. Subjects and methods: Thirty subjects of both genders (20 M/10 F), mean age 45.5±9.9 years ( M±SD), BMI 26.6±2.2 kg/m 2, with plasma cholesterol >5.17 and <7.76 mmol/l and plasma triglycerides <3.45 mmol/l, participated in the study. The study was performed after a wash-out period of 1 month and a run-in period of 1 month to stabilize patients on a standard diet (CHO 50%, fat 30%, protein 20%, fibre 20 g/day) plus placebo (maltodextrine plus aspartame 15 g/day). At the end of run-in, subjects were randomly assigned to receive sc-FOS (Actilight (R)) (10.6 g/day) or placebo (maltodextrine plus aspartame 15 g/day) with tea and/or coffee for a duration of 2 months and thereafter switched to the other treatment for additional 2 months. Plasma glucose, total and lipoprotein (VLDL, LDL, HDL) cholesterol and triglyceride concentrations were measured in the fasting state at the end of run-in and of each treatment period. At the end of the two treatment periods, patients consumed a standard test meal (protein 15%, carbohydrate 34%, fat 51%, kJ 3988) 1 h after the administration of 5.3 g of sc-FOS or placebo; plasma glucose, insulin, free fatty acid (FFA) and triglyceride responses to the test meal were evaluated. Results: No significant difference in fasting parameters was detected between the two treatments. After sc-FOS and placebo plasma cholesterol levels were, respectively, 6.47±0.70 and 6.44±0.78 mmol/l (n.s.) and plasma triglycerides were 1.53±0.71 and 1.56±0.53 mmol/l (n.s.). No significant differences were observed in cholesterol and triglyceride content of VLDL, LDL and HDL and in plasma Apo A1 levels; conversely, fasting plasma Lp(a) concentrations were significantly increased after sc-FOS (37±38 vs. 33±35 mg/dl; P<0.005). Postprandial responses of glucose, FFA and triglycerides were not significantly different between sc-FOS and placebo, while postprandial insulin response (incremental area) was significantly reduced after sc-FOS compared to placebo (14 490±7416 vs. 17 760±7710 pmol/l × 300 min; P<0.02). Conclusions: A moderate intake of sc-FOS has no major effects on lipid metabolism, both in the fasting and in the postprandial period, in individuals with mild hypercholesterolaemia. A small but significant increase of Lp(a) concentrations was observed with sc-FOS consumption together with a reduction of the postprandial insulin response; however, the clinical relevance of these small effects is unclear.