Effect of a low-fat diet on fatty acid composition in red cells, plasma phospholipids, and cholesterol esters : investigation of a biomarker of total fat intake

Background: The utility of fatty acids (FAs) as biomarkers of total fat intake is unknown.

Objective: We compared FA changes in red cells (RCs), plasma phospholipids (PLs), and cholesterol esters (CEs) in response to a low-fat diet (LFD) and a moderate-fat diet (MFD) and assessed whether individual or combination of FAs predict LFD.

Design: Postmenopausal women (n = 66) were randomly assigned to receive an LFD (17% of energy from fat) or an MFD (34% of energy from fat) for 6 wk. All foods were provided. FAs in diets and blood were determined by gas-liquid chromatography. FA changes between baseline and end of study were compared across diets by using t tests. FA predictors of an LFD were selected by logistic regression.

Results: Many FAs in RCs, PLs, and CEs responded differently to the 2 diets. Changes from baseline with an LFD for palmitic acid (16:0) (3–11% increase), behenic (22:0) and lignoceric (24:0) acids (3–20% decrease, in RCs and PLs only), cis-monounsaturated FA (MUFA) (25–35% increase), linoleic acid (18:2n–6) (11–13% decrease), trans octadecanoic acids (trans 18:1) (7–20% decrease), and n–6 highly unsaturated FA (HUFA) (2–8% increase) were significantly different from changes with an MFD. Individually, 18:2n–6 and trans 18:1 were strong predictors of an LFD [receiver operating characteristic (ROC) curves: 0.92–0.80). A logistic regression model with trans 18:1, 18:2n–6, and vaccenic acid (18:1n–7) predicted an LFD with high specificity and sensitivity (ROC curves: 0.99).

Conclusions: Saturated FA, cisMUFA, n–6 HUFA, and exogenous FAs greatly differed in their response to the LFD and MFD. Parallel responses were observed in RCs, PLs, and CEs. A model with a combination of FAs almost perfectly differentiated the consumption of 34% fat from that of 17% fat.

Cholesterol is necessary both for the toxic effect of Abeta peptides on vascular smooth muscle cells and for Abeta binding to vascular smooth muscle cell membranes

Accumulation of beta amyloid (Aβ) in the brain is central to the pathogenesis of Alzheimer's disease. Aβ can bind to membrane lipids and this binding may have detrimental effects on cell function. In this study, surface plasmon resonance technology was used to study Aβ binding to membranes. Aβ peptides bound to synthetic lipid mixtures and to an intact plasma membrane preparation isolated from vascular smooth muscle cells. Aβ peptides were also toxic to vascular smooth muscle cells. There was a good correlation between the toxic effect of Aβ peptides and their membrane binding. 'Ageing' the Aβ peptides by incubation for 5 days increased the proportion of oligomeric species, and also increased toxicity and the amount of binding to lipids. The toxicities of various Aβ analogs correlated with their lipid binding. Significantly, binding was influenced by the concentration of cholesterol in the lipid mixture. Reduction of cholesterol in vascular smooth muscle cells not only reduced the binding of Aβ to purified plasma membrane preparations but also reduced Aβ toxicity. The results support the view that Aβ toxicity is a direct consequence of binding to lipids in the membrane. Reduction of membrane cholesterol using cholesterol-lowering drugs may be of therapeutic benefit because it reduces Aβ-membrane binding.

Bivariate variance-component analysis, with application to systolic blood pressure and total cholesterol levels in the Framingham Heart Study

Background :
The correlations between systolic blood pressure (SBP) and total cholesterol levels (CHOL) might result from genetic or environmental factors that determine variation in the phenotypes and are shared by family members. Based on 330 nuclear families in the Framingham Heart Study, we used a multivariate normal model, implemented in the software FISHER, to estimate genetic and shared environmental components of variation and genetic and shared environmental correlation between the phenotypes. The natural logarithm of the phenotypes measured at the last visit in both Cohort 1 and 2 was used in the analyses. The antihypertensive treatment effect was corrected before adjustment of the systolic blood pressure for age, sex, and cohort.
Results :
The univariate correlation coefficient was statistically significant for sibling pairs and parent-offspring pairs, but not significant for spouse pairs. In the bivariate analysis, the cross-trait correlation coefficients were not statistically significant for all relative pairs. The shared environmental correlation was statistically significant, but the genetic correlation was not significant.
Conclusion :
There is no significant evidence for a close genetic correlation between systolic blood pressure and total cholesterol levels. However, some shared environmental factors may determine the variation of both phenotypes.

Identification and quantification of cholesterol oxides in foods

The types and levels of nine major cholesterol oxidation products was determined in a variety of foods. An estimate was made of the possible levels of cholesterol oxides in the Australian diet. These levels have been shown to cause endothelial damage in the coronary arteries of laboratory animals in previous studies. The health implications of these observations to humans is unknown.

Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods

Objectives: To determine the efficacy on plasma cholesterol-lowering of plant sterol esters or non-esterified stanols eaten within low-fat foods as well as margarine.
Design: Randomised, controlled, single-blind study with sterol esters and non-esterified plant stanols provided in breakfast cereal, bread and spreads. Study 1 comprised 12 weeks during which sterol esters (2.4 g) and stanol (2.4 g) -containing foods were eaten during 4 week test periods of cross-over design following a 4 week control food period. In Study 2, in a random order cross-over design, a 50% dairy fat spread with or without 2.4 g sterol esters daily was tested.
Subjects: Hypercholesterolaemic subjects; 22 in study 1 and 15 in study 2.
Main outcome measures: Plasma lipids, plasma sterols, plasma carotenoids and tocopherols.
Results: Study 1¾median LDL cholesterol was reduced by the sterol esters (-13.6%; P<0.001 by ANOVA on ranks; P<0.05 by pairwise comparison) and by stanols (-8.3%; P=0.003, ANOVA and <0.05 pairwise comparison). With sterol esters plasma plant sterol levels rose (35% for sitosterol, 51% for campesterol; P<0.001); plasma lathosterol rose 20% (P=0.03), indicating compensatory increased cholesterol synthesis. With stanols, plasma sitosterol fell 22% (P=0.004), indicating less cholesterol absorption. None of the four carotenoids measured in plasma changed significantly. In study 2, median LDL cholesterol rose 6.5% with dairy spread and fell 12.2% with the sitosterol ester fortified spread (P=0.03 ANOVA and <5% pairwise comparison).
Conclusion: 1. Plant sterol esters and non-esterified stanols, two-thirds of which were incorporated into low-fat foods, contributed effectively to LDL cholesterol lowering, extending the range of potential foods. 2. The LDL cholesterol-raising effect of butter fat could be countered by including sterol esters. 3. Plasma carotenoids and tocopherols were not reduced in this study.

Oat beta-glucan lowers total and LDL-cholesterol

Several soluble polysaccharides have been shown to have cholesterol-lowering properties and to have a role in prevention of heart disease. Major sources of one such polysaccharide (beta-glucan) are oats and barley. The aim of this study was to examine the effects on plasma lipid concentrations when beta-glucan derived from a fractionated oat preparation was consumed by people with elevated plasma lipids. A single-blind, crossover design compared plasma cholesterol, triglycerides, high density lipoproteins and low density lipoproteins (LDLs) in 14 people; in the order of low, high and low beta-glucan supplemented diets, each of three weeks duration. For the high beta-glucan diet, an average intake of 7 g per day was consumed from cereal, muffins and bread. The background diet remained relatively constant over the three test periods. Differences during the interventions were calculated by one-way repeated measures analysis of variance. Where treatments were found to be significantly different, pairwise multiple comparison procedures (Tukey Test) were carried out between the high beta-glucan and each of the low beta-glucan phases and there was a highly significant difference between treatments for plasma cholesterol (P = 0.009) and for LDL-cholesterol concentrations (P < 0.001). The differences in plasma cholesterol (6.42 +/- 0.7, 6.14 +/- 0.53, 6.44 +/- 0.67 mmol/L) and LDL-cholesterol (4.59 +/- 0.59, 4.17 +/0.58, 4.52 +/- 0.65 mmol/L) between high beta-glucan and each of the low beta-glucan treatments were significant (P < 0.05). The effect on LDLs (9% lower) is among the highest reported. The results of this study confirm that beneficial reductions in plasma cholesterol and LDL-cholesterol concentrations can be obtained with beta-glucan incorporated into a variety of foods.

The raft-promoting property of virion-associated cholesterol, but not the presence of virion-associated brij 98 rafts, is a determinant of human immunodeficiency virus type 1 infectivity

Lipid rafts are enriched in cholesterol and sphingomyelin and are isolated on the basis of insolubility in detergents, such as Brij 98 and Triton X-100. Recent work by Holm et al. has shown that rafts insoluble in Brig 98 can be found in human immunodeficiency virus type 1 (HIV-1) virus-like particles, although it is not known whether raft-like structures are present in authentic HIV-1 and it is unclear whether a virion-associated raft-like structure is required for HIV replication. Independently, it was previously reported that virion-associated cholesterol is critical for HIV-1 infectivity, although the specific requirement of virion cholesterol in HIV-1 was not examined. In the present study, we have demonstrated that infectious wild-type HIV-1 contains Brij 98 rafts but only minimal amounts of Triton X-100 rafts. To directly assess the functional requirement of virion-associated rafts and various features of cholesterol on HIV-1 replication, we replaced virion cholesterol with exogenous cholesterol analogues that have demonstrated either raft-promoting or -inhibiting capacity in model membranes. We observed that variable concentrations of exogenous analogues are required to replace a defined amount of virion-associated cholesterol, showing that structurally diverse cholesterol analogues have various affinities toward HIV-1. We found that replacement of 50% of virion cholesterol with these exogenous cholesterol analogues did not eliminate the presence of Brij 98 rafts in HIV-1. However, the infectivity levels of the lipid-modified HIV-1s directly correlate with the raft-promoting capacities of these cholesterol analogues. Our data provide the first direct assessment of virion-associated Brij 98 rafts in retroviral replication and illustrate the importance of the raft-promoting property of virion-associated cholesterol in HIV-1 replication.