Search

Background and Aim: Few studies have explored the possible plasma cholesterol lowering effects of rye consumption. The aim of this secondary analysis in the SYSDIET study was to investigate the association between plasma alkylresorcinols (AR), a biomarker for whole grain wheat and rye intake, and blood lipid concentrations in a population with metabolic syndrome. Furthermore, we analyzed the associations between the AR C17:0/C21:0 ratio, a suggested marker of the relative intake of whole grain/bran rye, and blood lipid concentrations., Methods: Participants were 30-65 years of age, with body mass index (BMI) 27-40 kg/m2 and had metabolic syndrome. Individuals were recruited through six centers in the Nordic countries and randomized either to a healthy Nordic diet (ND, n = 93), rich in whole grain rye and wheat, as well as berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products, or a control diet (n = 65) for 18/24 weeks. Associations between total plasma AR concentration and C17:0/C21:0 homologue ratio and blood lipids were investigated in pooled (ND + control group) regression analyses at 18/24 weeks adjusted for baseline value for the dependent variable, age, BMI and statin use., Results: When adjusted for confounders, total plasma AR at 18/24 weeks was not significantly associated with blood lipids but the AR ratio C17:0/C21:0 was inversely associated with LDL cholesterol concentrations (B (95% CI): -0.41 (-0.80 to -0.02)), log LDL/HDL cholesterol ratio (-0.20 (-0.37 to -0.03)), log non-HDL cholesterol (-0.20 (-0.37 to -0.03)), log apolipoprotein B (-0.12 (-0.24 to 0.00)) and log triglyceride concentrations (-0.35 (-0.59 to -0.12))., Discussion: Increased proportion of whole grain rye, reflected by a biomarker, in the diet is associated with favorable blood lipid outcomes, a relationship that should be further investigated., Trial Registration: ClinicalTrials.gov NCT00992641.

Background: Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome., Methods: We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m(-2) , 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids., Results: Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L(-1) 95% CI -0.35; -0.01, P = 0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37 ng L(-1) , P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, -0.23, -0.41; -0.05, P = 0.012) were associated with IL-1 Ra., Conclusions: Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation., (© 2013 The Association for the Publication of the Journal of Internal Medicine.)

A high-throughput proton (1H) nuclear magnetic resonance (NMR) metabonomics approach is introduced to characterise systemic metabolic phenotypes. The methodology combines two molecular windows that contain the majority of the metabolic information available by 1H NMR from native serum, e.g. serum lipids, lipoprotein subclasses as well as various low-molecular-weight metabolites. The experimentation is robotics-controlled and fully automated with a capacity of about 150-180 samples in 24 h. To the best of our knowledge, the presented set-up is unique in the sense of experimental high-throughput, cost-effectiveness, and automated multi-metabolic data analyses. As an example, we demonstrate that the NMR data as such reveal associations between systemic metabolic phenotypes and the metabolic syndrome (n = 4407). The high-throughput of up to 50,000 serum samples per year is also paving the way for this technology in large-scale clinical and epidemiological studies. In contradiction to single 'biomarkers', the application of this holistic NMR approach and the integrated computational methods provides a data-driven systems biology approach to biomedical research.

Several studies indicate that light-to-moderate alcohol consumption is associated with a low prevalence of coronary heart disease. An increase in high-density lipoprotein (HDL) cholesterol is associated with alcohol intake and appears to account for approximately half of alcohol's cardioprotective effect. In addition to changes in the concentration and composition of lipoproteins, alcohol consumption may alter the activities of plasma proteins and enzymes involved in lipoprotein metabolism: cholesteryl ester transfer protein, phospholipid transfer protein, lecithin:cholesterol acyltransferase, lipoprotein lipase, hepatic lipase, paraoxonase-1 and phospholipases. Alcohol intake also results in modifications of lipoprotein particles: low sialic acid content in apolipoprotein components of lipoprotein particles (e.g., HDL apo E and apo J) and acetaldehyde modification of apolipoproteins. In addition, "abnormal" lipids, phosphatidylethanol, and fatty acid ethyl esters formed in the presence of ethanol are associated with lipoproteins in plasma. The effects of lipoproteins on the vascular wall cells (endothelial cells, smooth muscle cells, and monocyte/macrophages) may be modulated by ethanol and the alterations further enhanced by modified lipids. The present review discusses the effects of alcohol on lipoproteins in cholesterol transport, as well as the novel effects of lipoproteins on vascular wall cells.

Objective: The aim of the study was to examine the impact of the leucine7 to proline7 (Leu7Pro) polymorphism of the NPY gene on postprandial (PP) lipemia, post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities, and the response of serum lipids to a reduced fat diet., Design and Subjects: Seven middle-aged obese subjects with Leu7Pro genotype were matched with seven subjects with Leu7Leu genotype for gender, age, apolipoprotein E phenotype and BMI. These 14 subjects participated in the oral 8 h fat tolerance test. Sixty-eight slightly obese middle-aged subjects (10 with the Leu7Pro genotype) had participated in intervention studies and consumed a reduced fat diet for 8 weeks., Results: There were no statistically significant differences in PP areas under the curve of plasma total triglycerides (TG), chylomicron TG, VLDL-TG or insulin between the genotype groups. The TG-to-cholesterol (C) ratio in VLDL was significantly lower in the subjects with Leu7Pro genotype compared to those with the Leu7Leu genotype at time points 30 min and 1 h in the fat tolerance test. Heparin-induced activities of LPL or HL or the response of serum total or LDL-C to the reduced fat diet did not differ between the groups., Conclusions: The NPY genotype neither affects the magnitude of postprandial lipemia induced by a fat tolerance test nor the response of serum total lipids or lipids in different lipoprotein classes to the reduced fat diet. However, this preliminary study suggests that there might be compositional differences in the lipoprotein particles between the genotype groups that affect postprandial lipid metabolism., Sponsorship: The Council for Health Sciences of the Academy of Finland, Kuopio University Hospital and the National Technology Agency, Finland.

Background: The genetic variance determining plasma lipid and lipoprotein concentrations may modify individual responsiveness to alterations in dietary fat and cholesterol content., Objective: The aim was to examine the role of apolipoprotein (apo) B DNA polymorphisms in responsiveness of plasma lipids and lipoproteins to diet., Design: A controlled dietary intervention study was conducted in 44 healthy, middle-aged subjects with a 3-mo baseline, a 1-mo fat-controlled, a 1-mo high-fat, and a 1-mo habitual diet period. We also conducted a meta-analysis of all published dietary trials, including our own., Results: In our own dietary study, the apo B XbaI restriction-site polymorphism affected the responsiveness to diet of the plasma LDL-cholesterol concentration (P < 0.05, repeated-measures analysis of variance). Especially during the high-fat diet, homozygous absence of the XbaI restriction site (X(-)/X(-)) was associated with a greater increase in LDL cholesterol (44 +/- 5%) than was X(+)/X(+) (27 +/- 7%) or X(+)/X(-) (40 +/- 5%). The high-fat diet also induced a larger increase in plasma LDL cholesterol in subjects with the R(-)/R(-) genotype (homozygous absence of the EcoRI restriction site) (59 +/- 10%) than in those with the R(+)/R(-) (39 +/- 6%) or R(+)/R(+) (36 +/- 4%) genotype. The M(+)/M(+) genotype (homozygous presence of the MspI restriction site) was also more responsive (41 +/- 3% increase in LDL cholesterol) than the M(+)/M(-) genotype (27 +/- 10% increase). The meta-analysis supported the finding of the significant role of the EcoRI and MspI polymorphisms, but not that of the XbaI polymorphism., Conclusions: The present study indicated that the apo B EcoRI and MspI polymorphisms are associated with responsiveness to diet.

Obesity is associated with adverse changes in plasma lipoprotein metabolism, but it is not known completely how this association is modified by genetic factors. We assessed the contribution of obesity to serum lipid and lipoprotein levels and lipid metabolizing enzyme activities by examining 23 identical twin pairs (9 male, 14 female) who had, on the average, an 18-kg intrapair difference in BW. Compared with lean co-twins, obese co-twins had approximately 20% higher low-density lipoprotein (LDL) cholesterol (P < 0.01), 20% lower high-density lipoprotein2 cholesterol (P = 0.010), and 90% (men) or 35% (women) higher (P < or = 0.06) total, very-low-density lipoprotein and LDL triglycerides. The pairs were divided into subgroups by the gender-specific median value of abdominal visceral fat (AVF) area in the obese co-twin and by apolipoprotein E 4 phenotype. The intrapair differences in serum cholesterol fractions were similar in twin pairs with high or low AVF, whereas only high AVF pairs showed significant differences in triglyceride fractions. The greatest intrapair differences in total, very-low-density lipoprotein and LDL triglycerides were observed in apolipoprotein E 4-positive pairs expressing high AVF. Compared with lean co-twins, lecithin cholesterol acyltransferase activity was 18% higher (P < 0.001) and hepatic lipase activity was 38% higher (P = 0.016) in obese co-twins with high AVF. When genetic factors are identical, obesity is associated with an atherogenic lipid profile, especially in subjects with high visceral fat accumulation.

Alcohol use is known to increase high-density lipoprotein (HDL) cholesterol, which is at least in part mediated by the alcohol-induced reduction in plasma cholesteryl ester transfer protein (CETP) activity and mass. We have shown that the high plasma HDL concentration reduces the CETP-mediated net mass transfer of cholesteryl esters from HDL to very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), or even reverses the direction of transfer in plasma incubations. Therefore, we studied the effect of lipoprotein composition on lipid net mass transfers in 14 male alcohol abusers and nine male control subjects by incubating plasma for up to 2 h. The cholesteryl ester net mass transfer in the alcohol abusers was mainly predicted by the VLDL and LDL lipid composition in multiple linear regression, while the HDL composition was the main factor in the controls. The observed difference in the effect of the lipoprotein composition on cholesteryl ester net mass transfer support our previous finding in rabbits that CETP binding to lipoproteins may differ during ethanol oxidation. The results suggest that ethanol oxidation induces alterations which may affect the binding of CETP to lipoproteins.

The effect of apolipoprotein (apo) E phenotype on the concentration and chemical composition of plasma lipoproteins was studied in 73 male alcohol abusers and 50 male controls. The apo E phenotype was confirmed by genotyping to avoid possible effects of posttranslational modifications by alcohol or its metabolites. The lipid and protein concentrations of both intermediate density lipoprotein and low density lipoprotein were lower among the alcohol abusers than among the controls, those with E4 having the highest low density lipoprotein masses in both groups. In the alcohol abusers with E4 only the high density lipoprotein (HDL)-2 lipid and protein concentrations were higher than in the controls with respective phenotype group, whereas both HDL2 and HDL3 were higher in alcohol abusers with other apo E phenotypes, suggesting that apo E modulates the alcohol-effect on HDL subfractions. This effect was not explained by cholesteryl ester transfer protein activity, which was lower in the alcohol abusers (25 to 34%, p < 0.01), but without significant difference between the apo E groups. In conclusion, alcohol abuse does not cause major changes in the electric charge of apo E in humans. Heavy alcohol intake seems to have a beneficial effect on plasma lipids and lipoproteins, regardless of the apo E phenotype, but the modulation of the alcohol-induced increase in HDL by apo E phenotype should be taken into consideration in future studies.

The effects of palmitic and stearic acid-enriched diets on serum lipids, lipoproteins, apolipoproteins (apo) A-I and B, and plasma cholesteryl ester transfer protein (CETP) activity were examined in 12 healthy young women. Subjects followed the two experimental diets for 4 weeks according to a randomized crossover design. Both experimental diet periods were preceded by consumption of a baseline diet for 2 weeks. The diets provided 37% of total energy intake (E%) as fat, and differed only with respect to fatty acid composition. There was a substitution of 5E% of palmitic acid or stearic acid in the experimental diets for 5E% of monounsaturated fatty acids in the baseline diet. After the palmitic acid diet, serum total and high-density lipoprotein (HDL) cholesterol and apo A-I concentrations were higher (8%, P = .015, 9%, P = .040, and 11%,P = .011, respectively) and mean serum low-density lipoprotein (LDL) cholesterol concentration tended to be higher (8%, P = .077) as compared with values after the stearic acid diet. Plasma CETP activity increased in the palmitic acid diet as compared with the stearic acid diet (12%, P = .006). In conclusion, palmitic acid and stearic acid-enriched diets had different effects on serum lipids and lipoproteins and also on plasma CETP activity in young healthy women.

Fifteen healthy young women were fed diets enriched to 4% of energy with either palmitic acid (as palm oil) or lauric acid (as coconut oil). A randomized crossover study design was used so that subjects followed the two experimental diets for 4 wk, both preceded by consumption of a baseline diet for 2 wk. The experimental diets differed only with respect to the fatty acid composition: there was a substitution of 4% of energy intake with palmitic acid or lauric acid in the experimental diets for 4% of energy as monoenes in the baseline diet. There were no differences in the concentration of serum total or lipoprotein lipids, apolipoproteins A-I and B, and lipoprotein (a) or plasma cholesteryl ester transfer protein activity between the experimental diet periods. The VLDL cholesterol concentration (0.38 +/- 0.05 vs. 0.51 +/- 0.05 mmol/L, means +/- SEM, P = 0.01] and plasma cholesteryl ester transfer protein activity [78 +/- 5 vs. 88 +/- 6 mumol/(h.L), P = 0.007) were greater at the end of the lauric acid diet period than at the end of the preceding baseline diet period. No differences were found in glucose effectiveness, insulin sensitivity index or insulin secretion measured by the intravenous glucose tolerance test (Minimal Model method). In conclusion, in terms of serum lipids, lipoproteins, and glucose metabolism, palmitic acid was equal to lauric acid at 4% of total energy intake exchange, and both of these saturated fatty acids were comparable to a 4% of total energy intake exchange with monoenes in healthy young women.

A new method is presented for absolute quantitation of lipid and protein contents of human lipoproteins directly from plasma. The method enables complete lipoprotein lipid profiles to be obtained in a total time of less than one hour. Absolute concentrations of triglycerides, phospholipids, total cholesterol, free cholesterol, esterified cholesterol, total proteins, and total masses can be estimated for the very low density (VLDL) and low density (LDL) lipoprotein fractions. For the high density lipoprotein (HDL) fraction all components except triglycerides can be quantitated. The method is a combination of 1H NMR spectroscopy and a sophisticated lineshape fitting analysis technique. In this paper we present the calibration of the method using 15 plasma samples followed by a double-blind test of 51 plasma samples from 43 individuals. In total, 66 plasma samples were analyzed. Comparison of the 1H NMR-based results with the data of the biochemical assays showed excellent agreement; the correlation coefficient for VLDL triglycerides was 0.98, for LDL cholesterol 0.88, and for HDL cholesterol 0.93. This method can be directly integrated to many kinds of biomedical NMR studies to offer additional biochemically important quantitative lipoprotein information, the measurement of which is usually too laborious by conventional biochemical methods and too high-priced to be adapted into the study protocols. Moreover, the method also has considerable potential to be developed for a routine clinical assay.

The purpose of this work was two-fold. In the first instance, 1H NMR spectra of the ultracentrifuged lipoprotein fractions (VLDL, LDL and HDL) from six volunteers with different clinical conditions were measured. The methylene regions of the experimental spectra were modelled in the frequency domain using non-linear lineshape fitting analyses. In this way the resolvable Lorentzian component structures of the methylene regions of these lipoprotein fraction spectra could be determined. Second, the lipoprotein fraction analyses were used to construct simplified component structures, which interpreted the lipoprotein fraction spectra well, and were feasible to use in the total plasma spectra analyses. The considerable overlap problem of the resonances was properly handled in this way. The NMR-based relative amounts of the lipoproteins (relative integrated intensities of the lipoprotein model signals) obtained were compared to the biochemically resolved relative molar percentages of the lipoprotein fractions and also of the lipid contents between the lipoprotein complexes. It was noticed that nearly all correlations were extremely good. Thus, it is suggested that the developed methodology could be used as a fast method to predict the relative amounts of the lipoproteins and also possibly the relative lipid contents between the major lipoprotein categories directly from the proton NMR spectrum of a total blood plasma sample. Furthermore, if internal or external reference for the integrated intensities of the proton NMR resonances were used, it should also be possible to obtain the absolute amounts of these quantities.

1. Hepatic lipogenesis in vivo and the activities of enzymes associated with fatty acid synthesis in the liver were studied in rats fed for 21 days on liquid diets containing ethanol. 2. The ethanol-fed rats developed a moderate hepatic triacylglycerol accumulation during this period. When carbohydrate was replaced by ethanol in the diet, the rate of fatty acid synthesis was slower in the ethanol-fed rats on low-, medium- and high-fat diets than in the appropriate controls. However, when the fat/carbohydrate ratio was kept the same in the ethanol-fed and control rats, ethanol had no influence on the rate of fatty acid synthesis. 3. Glucose 6-phosphate dehydrogenase activity was lower in the ethanol-fed group. ;Malic' enzyme activity did not change during the ethanol treatment when the fat/carbohydrate ratio was kept unchanged. 4. The ATP citrate lyase activity was lower in the ethanol-fed rats on all diets, whereas acetyl-CoA synthetase activity was independent of the composition of the control diet, but was lower in the ethanol-fed rats, in which the concentration of the active form of pyruvate dehydrogenase was also lower. 5. It is concluded that hepatic fatty acid synthesis does not play any major role in ethanol-induced triacylglycerol accumulation. Careful design of the diets is necessary to reveal the specific effects of ethanol on the enzymes associated with lipogenesis.