Several previous epidemiological studies from developed countries have shown that an unhealthy dietary pattern affects plasma lipid levels and inflammation biomarkers. We assessed the cross-sectional associations between dietary patterns and cardiovascular risk factors among 961 adults from a multi-city cohort in South America. We conducted a principal component analysis to derive dietary patterns. As outcomes, we examined plasma levels of apo A-I, apo B, high-sensitivity C-reactive protein (hs-CRP), LDL-, HDL- and serum total cholesterol and TAG. The crude and adjusted changes in each outcome were estimated for quartiles of dietary patterns using multivariable linear regression models. The prudent pattern (PP) characterised by higher intake of fruits, vegetables, fish, seafood, whole cereal and low-fat dairy products was associated with reduced plasma concentrations of apo B (−8·5 mg/l), total cholesterol (−18·8 mg/dl) and LDL-cholesterol (−16·5 mg/dl) and hs-CRP (−1·6 mg/l) in men. In women also reduced plasma concentrations of apo B (−6·6 mg/l), total (−12·0 mg/dl) and LDL (−9·3 mg/dl). The ‘Western-like’ pattern characterised by higher intake of eggs, pastry and cakes, pizza, snacks, refined grains, red meat, vegetable oils and poultry was not significantly associated with any of the selected serum lipid or inflammatory biomarkers. The explained variances were 10·3 and 7·4 %, respectively. The PP was associated with better lipid profile, mainly lower atherogenic particles (apo B) and LDL-cholesterol and serum total cholesterol. This study provides possible evidence of a prudent diet in South American populations to help reduce the burden of CVD.

Several studies have reported association of altered levels of lipids and some trace elements with risk factors for cardiovascular disease development in adulthood. Accordingly, the present study aimed to determine the relationship among the serum levels of copper (Cu), zinc (Zn), lipids, lipoproteins and apolipoproteins in preterm infants through an assessment of atherogenic indices shortly after birth. Blood samples were collected within 20 min of birth from 45 preterm infants with gestational ages ranging from 32 to 35 weeks. Serum Cu, Zn, total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels were measured, and the TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were calculated. Upon determining the correlation between the levels of Cu, Zn and these indices of lipid metabolism, triglyceride (TG) and Cu were found to correlate negatively with birth weight (BW) and the standard deviation (s.d.) score for body weight. Furthermore, Cu levels correlated positively with the TG level and TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios and negatively with the HDLc level and HDLc/apoA1 ratios. However, a stepwise multiple regression analysis indicated that the s.d. score for BW and TG level were significant independent determinants of the Cu level. In contrast, Zn did not correlate with any of these indices. In conclusion, intrauterine growth restriction and the TG level at birth influence Cu levels in preterm infants, whereas atherogenic indices do not affect this parameter.

Evidence suggests that breastfeeding during infancy lowers the risk of metabolic syndrome (MS) and its attendant risk factors in adult life. To investigate the influence of feeding type on the risk factors of MS, we assessed insulin sensitivity and lipid and apolipoprotein metabolism in preterm infants. Blood samples were collected from preterm infants at the time of discharge. Infants were separated into two groups: a breast milk (BM) group receiving ⩾90% of their intake from BM, and a mixed-fed (MF) group receiving ⩾50% of their intake from formula. The following indices were then compared between the two groups. Blood glucose and serum insulin levels were used to calculate the quantitative insulin sensitivity check index (QUICKI). We also measured serum total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels, and the ratios of TC/HDLc, LDLc/HDLc and apoB/apoA1. The mean gestational age was 32.9 weeks at birth, and blood samples were collected at a mean corrected age of 37.4 weeks. There were 22 infants in the BM group and 19 in the MF group. QUICKI was significantly higher in the BM group. TC, HDLc and apoA1 were not significantly different between the groups, but LDLc and apoB levels were significantly higher in the BM group. The TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were significantly higher in the BM group. In preterm infants, the type of feeding exposure in the early postnatal period may influence glucose, lipid and apolipoprotein metabolism, and affect markers of MS.

Consumption of a Mediterranean diet (MD) and genetic variation in the glucokinase regulatory protein (GCKR) gene have been reported to be associated with TAG and glucose metabolism. It is uncertain whether there is any interaction between these factors. Therefore, the aims of the present study were to test the association of adherence to a MD and rs780094 (G>A) SNP in the GCKR gene with the markers of cardiometabolic risk, and to investigate the interaction between genetic variation and MD adherence. We studied 20 986 individuals from the European Prospective Investigation into Cancer (EPIC)-Norfolk study. The relative Mediterranean Diet Score (rMED: range 0–18) was used to assess MD adherence. Linear regression was used to estimate the association between the rMED, genotype and cardiometabolic continuous traits, adjusting for potential confounders. In adjusted analyses, we observed independent associations of MD adherence and genotype with cardiometabolic risk, with the highest risk group (AA genotype; lowest rMED) having higher concentrations of TAG, total cholesterol and apoB (12·5, 2·3 and 3·1 %, respectively) v. those at the lowest risk (GG genotype; highest rMED). However, the associations of MD adherence with metabolic markers did not differ by genotype, with no significant gene–diet interactions for lipids or for glycated Hb. In conclusion, we found independent associations of the rMED and of the GCKR genotype with cardiometabolic profile, but found no evidence of interaction between them.

The present randomised parallel study assessed the impact of adding MUFA to a dietary portfolio of cholesterol-lowering foods on the intravascular kinetics of apoAI- and apoB-containing lipoproteins in subjects with dyslipidaemia. A sample of sixteen men and postmenopausal women consumed a run-in stabilisation diet for 4 weeks. Subjects were then randomly assigned to an experimental dietary portfolio either high or low in MUFA for another 4 weeks. MUFA substituted 13·0 % of total energy from carbohydrate (CHO) in the high-MUFA dietary portfolio. Lipoprotein kinetics were assessed after the run-in and portfolio diets using a primed, constant infusion of [2H3]leucine and multicompartmental modelling. The high-MUFA dietary portfolio resulted in higher apoAI pool size (PS) compared with the low-MUFA dietary portfolio (15·9 % between-diet difference, P= 0·03). This difference appeared to be mainly attributable to a reduction in apoAI fractional catabolic rate (FCR) after the high-MUFA diet ( − 5·6 %, P= 0·02 v. pre-diet values), with no significant change in production rate. The high-MUFA dietary portfolio tended to reduce LDL apoB100 PS compared with the low-MUFA dietary portfolio ( − 28·5 % between-diet difference, P= 0·09), predominantly through an increase in LDL apoB100 FCR (23·2 % between-diet difference, P= 0·04). These data suggest that adding MUFA to a dietary portfolio of cholesterol-lowering foods provides the added advantage of raising HDL primarily through a reduction in HDL clearance rate. Replacing CHO with MUFA in a dietary portfolio may also lead to reductions in LDL apoB100 concentrations primarily by increasing LDL clearance rate, thus potentiating further the well-known cholesterol-lowering effect of this diet.

Genome-wide association analysis on monozygotic twin-pairs offers a route to discovery of gene–environment interactions through testing for variability loci associated with sensitivity to individual environment/lifestyle. We present a genome-wide scan of loci associated with intra-pair differences in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions for both twins. We found one locus associated with intra-pair differences in high-density lipoprotein cholesterol, rs2483058 in an intron of SRGAP2, where twins carrying the C allele are more sensitive to environmental factors (P = 3.98 × 10−8). We followed up the association in further genotyped monozygotic twins (N = 1,261), which showed a moderate association for the variant (P = 0.200, same direction of an effect). In addition, we report a new association on the level of apolipoprotein A-II (P = 4.03 × 10−8).

Our aim was to determine whether meal fatty acids influence insulin and glucose responses to mixed meals and whether these effects can be explained by variations in postprandial NEFA and Apo, which regulate the metabolism of triacylglycerol-rich lipoproteins (Apo C and E). A single-blind crossover study examined the effects of single meals enriched in saturated fatty acids SFA), n-6 PUFA and MUFA on plasma metabolite and insulin responses. The triacylglycerol response following the PUFA meal showed a lower net incremental area under the curve than following the SFA and MUFA meals (P<0·007). Compared with the SFA meal, the PUFA meal showed a lower net incremental area under the curve for the NEFA response from initial suppression to the end of the postprandial period (180–480 min; P<0·02), and both PUFA and MUFA showed a lower net incremental glucose response (P<0·02), although insulin concentrations were similar between meals. The pattern of the Apo E response was also different following the SFA meal (P<0·02). There was a significant association between the net incremental NEFA (180–480 min) and glucose response (rs=0·409, P=0·025), and in multiple regression analysis the NEFA response accounted for 24 % of the variation in glucose response. Meal SFA have adverse effects on the postprandial glucose response that may be due to greater elevations in NEFA arising from differences in the metabolism of SFA- v. PUFA- and MUFA-rich lipoproteins. Elevated Apo E responses to high-SFA meals may have important implications for the hepatic metabolism of triacylglycerol-rich lipoproteins.

A 38-residue protein associated with cholesteryl ester transfer inhibition has been identified in baboons (Papio sp.). The cholesteryl ester transfer inhibitor protein (CETIP) corresponds to the N-terminus of baboon apoC-I. Relative to CETIP, baboon apoC-I is a weak inhibitor of baboon cholesteryl ester transferase (CET). To study the structural features responsible for CET inhibition, CETIP was synthesized by solid-phase methods. Using sodium dodecyl sulfate (SDS) to model the lipoprotein environment, the solution structure of CETIP was probed by optical and 1H NMR spectroscopy. Circular dichroism data show that the protein lacks a well-defined structure in water but, upon the addition of SDS, becomes helical (56%). A small blue shift of 8 nm was observed in the intrinsic tryptophan fluorescence of CETIP in the presence of saturating amounts of SDS, suggesting that tryptophan-23 is not buried deeply in the lipid environment. The helical nature of CETIP in the presence of SDS was confirmed by upfield 1Hα secondary shifts and an average solution structure determined by distance geometry/simulated annealing calculations using 476 NOE-based distance restraints. The backbone (N-Cα-C=O) root-mean-square deviation of an ensemble of 17 out of 25 calculated structures superimposed on the average structure was 1.06 ± 0.30 Å using residues V4–P35 and 0.51 ± 0.17 Å using residues A7–S32. Although the side-chain orientations fit the basic description of a class A amphipathic helix, both intramolecular salt bridge formation and “snorkeling” of basic side chains toward the polar face play minor, if any, roles in stabilizing the lipid-bound amphipathic structure. Conformational features of the calculated structures for CETIP are discussed relative to models of CETIP inhibition of cholesteryl ester transferase.

Polymorphisms at the APOA1/C3/A4 gene cluster and the APOE gene have been extensively studied in order to examine their potential association with plasma lipid levels, coronary heart disease risk and more recently with inter-individual variability in response to dietary therapies. Although the results have not been uniform across studies, the current research supports the concept that variation at these genes explains a significant, but still rather small, proportion of the variability in fasting and postprandial plasma lipid responses to dietary interventions. This information constitutes the initial frame to develop panels of genetic markers that could be used to predict individual responsiveness to dietary therapy for the prevention of coronary heart disease. Future progress in this complex area will come from experiments carried out using animal models, and from carefully controlled dietary protocols in humans that should include the assessment of several other candidate gene loci coding for products that play a relevant role in lipoprotein metabolism (i.e. APOB, CETP, LPL, FABP2, SRBI, ABC1 and CYP7).

Raised plasma triacylglycerol is an independent risk factor for cardiovascular disease, and an understanding of factors which regulate the synthesis and degradation of lipoproteins which carry triacylglycerol in the blood may lead to novel approaches to the treatment of hypertriacylglycerolaemia. An active microsomal triacylglycerol transfer protein (MTP) is essential for the assembly of particles which transport triacylglycerol through the circulation. After absorption in the intestine, dietary fat and fat-soluble vitamins are incorporated into chylomicrons in the intestinal epithelial cells, and these lipoproteins reach the bloodstream via the lymphatic system. Patients with the rare genetic disorder, abetalipoproteinaemia, in which MTP activity is absent, present clinically with fat-soluble vitamin and essential fatty acid deficiency, indicating a key role for MTP in the movement of fat into the body. The triacylglycerol-rich lipoprotein found in fasting blood, VLDL, is assembled in the liver by an MTP-dependent process similar to chylomicron assembly, and transports triacylglycerol to extra-hepatic tissues such as adipose tissue and heart. In the absence of MTP activity, VLDL are not synthesized and only extremely low levels of triacylglycerol are present in the blood. Dietary components, including fat, cholesterol and ethanol, can modify the expression of the MTP gene and, hence, MTP activity. The present review summarizes current knowledge of the role of MTP in the assembly and secretion of triacylglycerol-rich lipoproteins, and the regulation of its activity in both animal and cell systems.

Apolipoprotein E (ApoE) genotype was determined in sixty-five subjects who had taken part in a 4-week randomized crossover trial to compare the effect of six mugs of black tea per day v. placebo on blood lipids and blood coagulation factors. Four ApoE genotype variants (seven E2/E3, forty-five E3/E3, twelve E3/E4 and one E4/E4) were found. ApoE allele frequency was within the range typical for Caucasian populations (ApoE-E2 5·4 %; ApoE-E3 83·8 %; ApoE-E4 10·8 %). Individuals bearing at least one E4 allele had substantially higher levels of serum total cholesterol, LDL cholesterol and triacylglycerols. Mean plasminogen activator inhibitor (PAI-1) activity was higher in ApoE-E4 allele-bearing individuals (E3/E4 + E4/E4, 11·89 (SE 1·27) U/ml; E3/E3, 9·19 (SE 0·80) U/ml; E2/E3, 7·21 (SE 1·04) U/ml, P values of E4-group v. E3 and E2 being respectively 0·093 and 0·030). These unexpected findings imply that elevated PAI-1 activity may be a hitherto unrecognized additional factor involved in the increased cardiovascular disease risk associated with apoE-E4 allele. The interactions between tea drinking and genotype were also examined. In the E3/E3 homozygotes, HDL-cholesterol was significantly reduced in the tea period (mean placebo 1·54 mmol/l v. mean tea 1·50 mmol/l, P = 0·027). In the E2/E3 group, triacylglycerol concentration was significantly reduced (mean placebo 1·18 mmol/l v. mean tea 1·09 mmol/l, P = 0·039). Tea also caused a significant decrease of PAI-1 activity in the subjects with E2/E3 genotype (mean placebo 7·21 U/ml v. mean tea 5.88 U/ml, P = 0·007). In the other two genotype groups, there was no significant effect of tea. The results indicate that tea drinking has a beneficial effect on some cardiovascular disease risk-associated factors, especially in E2 allele-bearing individuals. Dietary intervention may be particularly effective in population groups with certain genetic characteristics.

The present study examined the effects of Se, vitamin E and combined Se and vitamin E deficiencies in rats on plasma lipid, Lipoprotein and apolipoprotein (apo) concentrations. Deficiencies were induced by feeding rats the respective diets for 6 weeks. The study shows that Se deficiency results in increased concentrations of plasma cholesterol and apo E. Both could be explained by an increase in the HDL1 fraction. Vitamin E deficiency alone had no significant effect on plasma lipid, lipoprotein and apo concentrations. Se deficiency in combination with vitamin E deficiency leads to an increase in plasma LDL and apo B concentrations. These results point to the need for further investigations on the mechanism by which Se deficiency affects lipoprotein metabolism.

Thirty-eight male volunteers participated in a double-blind cross-over trial evaluating the effect of replacing the usual sources of saturated fat in the Dutch diet (animal fats and hydrogenated oils) by palm oil, which is virtually free of cholesterol and trans-fatty acids, on serum lipids, lipoproteins and apolipoproteins. Maximum (about 70%) replacement had no significant effect on serum total cholesterol or most lipoprotein fractions, but resulted in an 11% increase in serum high-density-lipoprotein (HDL)2-cholesterol relative to the control (P2 = 0.01). The palm-oil diet also caused an 8% decrease in low-density-lipoprotein (LDL):HDL2+HDL3-cholesterol ratio (P2 = 0.02) as well as a 9% decrease in triacylglycerols in the low-density-lipoprotein fractions (P2 = 0.01). Palm oil consumption resulted in a 4% increase in serum apolipoprotein AI (P2 = 0.008) and a 4% decrease in apolipoprotein B (P2 = 0.01) relative to the control diet; the B:AI apolipoprotein ratio was decreased by 8% (P2 < 0.0001). These results were not significantly affected by the different lipoprotein E phenotypes of the volunteers. Although the observed differences were relatively modest, the present study, nonetheless, indicates that dietary palm oil, when replacing a major part of the normal fat content in a Dutch diet, may slightly reduce the lipoprotein- and apolipoprotein-associated cardiovascular risk profiles

Traditional twin studies have resulted in higher concordance rates for premature coronary heart disease (CHD) in MZ than in DZ twin pairs. This is in agreement with strong evidence from several other studies, that genetic factors are of importance in the etiology of early onset CHD. Also, in a study of 291 Norwegian twin pairs the concordance rate for hypertension wa 0.36 in MZ and 0.08 in DZ pairs. Relationship between diseases and traditional gene markers have been extensively studied and several associations have been uncovered for CHD. Our group has developed a method to examine a possible permissive or restrictive effect of single genes on the degree of variation that environmental and/or life style factors can cause in a given parameter. This method for studying gene-environment interaction is based on the fact that MZ twins are identical with respect to genes, so that any difference between the two members of an MZ pair must necessarily be caused by environmental or life style factors. The possibility that a given gene influences the degree of variability in a parameter such as cholesterol is examined by comparing the within-pair difference in cholesterol level between MZ pairs possessing, and MZ pairs lacking the gene in question, and results of such studies will be presented. New possibilities to study restriction fragment length polymorphisms (RFLPs) at apolipoprotein loci have added a new dimension to research on genetics of CHD and hyperlipidemias. Association between apolipoprotein B, cholesterol and fasting triglyceride levels on one hand and DNA variation at the apolipoprotein B locus on the other has been found. We have studied RFLPs at apolipoprotein loci in twin families. The results are presented.