[Epidemiological study of acute poisoning cases treated at a Galician hospital between 2005 and 2008]. / Estudio epidemiológico de las intoxicaciones agudas atendidas en un hospital gallego entre 2005 y 2008.

A descriptive retrospective study of acute intoxication cases registered at the Complexo Hospitalario de Pontevedra (CHOP) between January 2005 and December 2008 was performed to find out the number and types of poisoning cases treated, their distribution according to patient's sex and age, chronology, type of toxic agents involved, intentionality, history, symptoms, clinical development, treatment and toxicological analysis used for diagnosis. Data were recorded using Clinica and IANUS software and consulting all paper records of patients with symptoms of poisoning. Data from a total of 1893 patients with a mean age of 35.6 ± 17.6 years (66% men) were included. Highest rates of poisoning were recorded on Saturdays and Sundays during the summer months (June, July and August). Drugs of abuse were the most common toxic agents (70.4%), ethyl alcohol accounting for 61% of these cases, which often involved males and with people with high degrees of dependency. In second place was poisoning resulting from the abuse of medical drugs, more commonly associated with females, and involving benzodiazepines in 73.2% of cases. The majority of these intoxications were intentional, and suicide attempts accounted for 18.8%. The problems most commonly resulting from the poisoning were neurological, and mortality rate was just 0.2%.

APOA1 and APOA4 gene polymorphisms influence the effects of dietary fat on LDL particle size and oxidation in healthy young adults.

We investigated whether APOA1 and APOA4 genotypes interact with diet to determine changes in LDL size and their susceptibility to oxidative modifications. A total of 97 healthy volunteers each consumed 3 diets for 4 wk: a SFA diet (38% fat, 20% SFA) followed by a low-fat and high-carbohydrate (CHO) diet (30% fat, 55% carbohydrate) or a monounsaturated fatty acid (MUFA) diet (38% fat, 22% MUFA) following a randomized crossover design. For each diet, we determined susceptibility to oxidative modifications and LDL size. To investigate the combined effects of the APOA1 G-76A and APOA4 Thr347Ser single nucleotide polymorphisms (SNP), we defined 4 combined genotype groups: GG/ThrThr, GG/ThrSer, GA/ThrThr, and GA/ThrSer. After participants consumed the CHO diet, there was a significant decrease in LDL size with respect to high-fat diets in GG homozygotes for the APOA1 G-76A SNP. However, LDL size did not differ in GA carriers among participants consuming the 3 diets. Carriers of the A allele for this polymorphism had smaller LDL size as well as increased susceptibility to oxidation after the SFA diet than the GG homozygous. Moreover, the interaction between the APO A1 and APOA4 genotypes revealed that individuals with the GA/ThrSer genotype had larger LDL particle size during consumption of the MUFA diet than when they consumed the CHO diet. No differences in LDL oxidation were found in this analysis. Our study supports the concept that SNP in APOA1and APOA4 genes influences atherogenic characteristics of LDL particles in response to diet.

A low-fat, high-complex carbohydrate diet supplemented with long-chain (n-3) fatty acids alters the postprandial lipoprotein profile in patients with metabolic syndrome.

Dietary fat intake plays a critical role in the development of metabolic syndrome (MetS). This study addressed the hypothesis that dietary fat quantity and quality may differentially modulate postprandial lipoprotein metabolism in MetS patients. A multi-center, parallel, randomized, controlled trial conducted within the LIPGENE study randomly assigned MetS patients to 1 of 4 diets: high-SFA [HSFA; 38% energy (E) from fat, 16% E as SFA], high-monounsaturated fatty acid [HMUFA; 38% E from fat, 20% E as MUFA], and 2 low-fat, high-complex carbohydrate [LFHCC; 28% E from fat] diets supplemented with 1.24 g/d of long-chain (LC) (n-3) PUFA (ratio 1.4 eicosapentaenoic acid:1 docosahexaenoic acid) or placebo (1.24 g/d of high-oleic sunflower-seed oil) for 12 wk each. A fat challenge with the same fat composition as the diets was conducted pre- and postintervention. Postprandial total cholesterol, triglycerides (TG), apolipoprotein (apo) B, apo B-48, apo A-I, LDL-cholesterol, HDL-cholesterol and cholesterol, TG, retinyl palmitate, and apo B in TG-rich lipoproteins (TRL; large and small) were determined pre- and postintervention. Postintervention, postprandial TG (P < 0.001) and large TRL-TG (P = 0.009) clearance began earlier and was faster in the HMUFA group compared with the HSFA and LFHCC groups. The LFHCC (n-3) group had a lower postprandial TG concentration (P < 0.001) than the other diet groups. Consuming the LFHCC diet increased the TG (P = 0.04), large TRL-TG (P = 0.01), TRL-cholesterol (P < 0.001), TRL-retinyl palmitate (P = 0.001), and TRL-apo B (P = 0.002) area under the curve compared with preintervention values. In contrast, long-term ingestion of the LFHCC (n-3) diet did not augment postprandial TG and TRL metabolism. In conclusion, postprandial abnormalities associated with MetS can be attenuated with LFHCC (n-3) and HMUFA diets. The adverse postprandial TG-raising effects of long-term LFHCC diets may be avoided by concomitant LC (n-3) PUFA supplementation to weight-stable MetS patients.

Chronic dietary fat intake modifies the postprandial response of hemostatic markers to a single fatty test meal.

BACKGROUND: Hemostasis is the result of a complex equilibrium between coagulation and fibrinolysis, and the influence of different dietary models on this equilibrium is not entirely known. OBJECTIVE: The objective was to compare the effects of the chronic intake of different dietary models on postprandial hemostasis. DESIGN: In a randomized crossover design, 20 healthy men consumed for 28 d each diets rich in monounsaturated fatty acids (MUFAs), saturated fatty acids (SFAs), and carbohydrates plus n-3 fatty acids (CHO/N3). Fasting and postprandial hemostatic factors (factor VII coagulant activity, plasminogen activator inhibitor-1, tissue-type plasminogen activator, d-dimer, and thromboxane B(2)) were measured; meal tests for the postprandial measures were based on butter, virgin olive oil, and walnuts for the SFA, MUFA, and CHO/N3 diets, respectively. RESULTS: There were no differences in the fasting variables after the dietary periods. After the 3 fatty meals were consumed, we observed an increase in thromboxane B(2) and d-dimer and a reduction in tissue plasminogen activator, irrespective of the dietary model. The MUFA or CHO/N3 meals lowered postprandial concentrations of factor VII coagulant activity, although the reduction was greater after the MUFA-enriched meal. The concentration of plasminogen activator inhibitor-1 was greater after the SFA meal than after the other 2 meals. CONCLUSIONS: The administration of a fatty meal induces a postprandial procoagulant tendency, irrespective of the type of fat consumed. However, the use of a dietary model rich in SFA creates a more procoagulant environment than does a model that includes MUFA or CHO/N3 as the source of fatty acids.

A monounsaturated fatty acid-rich diet reduces macrophage uptake of plasma oxidised low-density lipoprotein in healthy young men.

During atherogenesis, a pathological accumulation of lipids occurs within aortic intimal macrophages through uptake of plasma oxidised LDL (oxLDL). The aim of the present study was to determine whether macrophage uptake of plasma oxLDL and LDL susceptibility to oxidation may be determined by quantity and quality of dietary fat. Twenty healthy young men were subjected to three dietary periods, each lasting 4 weeks. The first was an SFA-enriched diet (38 % fat, 20 % SFA), which was followed by a carbohydrate (CHO)-rich diet (30 % fat, < 10 % SFA, 55 % CHO) or a MUFA olive oil-rich diet (38 % fat, 22 % MUFA) following a randomised cross-over design. After each diet period, LDL particles were oxidised with Cu ions to determine LDL susceptibility to oxidation and subsequently incubated with the U937-macrophage cell line to determine the percentage of uptake of plasma oxLDL. The shift from the MUFA diet to the SFA- or CHO-rich diets reduced the resistance of LDL particles to oxidation, decreasing lag time (P = 0.038) and increasing the propagation rate (P = 0.001). Furthermore, the MUFA-rich diet demonstrated reduced macrophage uptake of plasma oxLDL (P = 0.031) as compared with the SFA-rich diet. Finally, macrophage uptake of plasma oxLDL was correlated (r 0.45; P = 0.040) with total amount of conjugated dienes after LDL oxidation. Our data suggest that a MUFA-rich diet may have favourable effects on cardiovascular risk since it prevents the oxidative modifications of LDL and reduces macrophage uptake of plasma oxLDL.

Two independent apolipoprotein A5 haplotypes modulate postprandial lipoprotein metabolism in a healthy Caucasian population.

BACKGROUND: Apolipoprotein A5 (APOA5) plays an important role in plasma triacylglycerol (TG) homeostasis. Five polymorphisms (1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, and c.1259T>C) in the APOA5 gene define three common haplotypes (APOA5*1, APOA5*2, and APOA5*3) in Caucasian individuals. Our aim was to determine whether these haplotypes could modulate the postprandial response in young healthy males. DESIGN AND METHODS: Eighty-eight APO E3/3 volunteers [67 with (-1131T and 56C) APOA5*1 haplotype, 12 with (-1131C and 56C) APOA5*2 haplotype, and nine with (-1131T and 56G) APOA5*3 haplotype] underwent a fat load test consisting of the consumption of 1 g of fat per kilogram body weight and 60,000 IU vitamin A. Blood samples were taken at time 0, at every hour until the sixth hour, and at every 2.5 h until the 11th hour. Total plasma cholesterol (C) and TG, and C, TG, apolipoprotein B-100, apolipoprotein B-48, and retinyl palmitate in lipoprotein fractions were determined. RESULTS: Subjects with the APOA5*2 and APOA5*3 haplotypes had a higher area under the curve of total plasma TG (P = 0.03), large TG-rich lipoprotein (TRL)-TG (P = 0.02), small TRL-TG (P = 0.04), small TRL-C (P = 0.04), large TRL-C (P = 0.03), and small apolipoprotein B100 (P = 0.04) than subjects with the APOA5*1 haplotype. CONCLUSIONS: Our findings show that the presence of the APOA5*2 and APOA5*3 haplotypes in the APOA5 gene is associated with a higher postprandial response that could be involved in the higher risk of coronary heart disease associated with the 56G and -1131C alleles.

The APOB -516C/T polymorphism has no effect on lipid and apolipoprotein response following changes in dietary fat intake in a healthy population.

Our goal was to determine whether the presence of the -516C/T polymorphism in the APOB gene promoter modifies the lipid response to changes in the amount and quality of dietary fat. We studied 97 young healthy volunteers (70 males and 27 females), 62 homozygotes for the -516C allele (C/C) (47 males and 15 females), 34 heterozygotes for the -516T allele (C/T) (22 males and 12 females) and one male homozygote for the -516T allele (T/T). Subjects consumed three different diets in successive 4-week dietary periods. During the first 28 days, all subjects consumed a saturated fatty acid (SFA)-rich diet (38% fat and 20% SFA). Then, using a randomized crossover design, subjects were assigned a carbohydrate (CHO)-rich diet (30% fat and 55% carbohydrate) or a monounsaturated fatty acid (MUFA)-rich diet (38% fat and 22% MUFA). At the end of each dietary period, plasma concentrations of triacylglycerols and of total, LDL, and HDL cholesterol were measured. No differences in plasma lipid and apolipoprotein response were found after changes in dietary fat intake in relation to the -516C/T polymorphism in our study population. In conclusion, our data suggest that the APOB -516C/T polymorphism has no effect on the lipid profile after changes in dietary fat intake in a healthy population.

A single nucleotide polymorphism of the apolipoprotein A-V gene -1131T>C modulates postprandial lipoprotein metabolism.

The Apolipoprotein A-V (apoA-V) gene promoter polymorphism -1131T>C modulates triacylglycerol (TG) concentrations. We evaluate whether this polymorphism could be involved in the interindividual variability observed during postprandial lipemia. Fifty-one healthy apo E3E3 male volunteers [12 with -1131CC/CT genotype, and 39 with -1131TT genotype] underwent a Vitamin A fat-load test consisting of 1g of fat/kg body weight and 60,000IU of Vitamin A. Blood samples were taken at time 0 and every hour until the 6th and every 2h and 30 min until the 11th. Cholesterol (Chol) and TG were determined in plasma and Chol, TG, ApoB-100, ApoB-48, and retinyl palmitate (RP) were determined in lipoprotein fractions. Data of postprandial lipemia revealed that subjects with the -1131CT/CC genotype had a higher postprandial response of total plasma TG (p=0.043), large triacylglycerol-rich lipoproteins-TG (TRL-TG) (p=0.002), large TRL-Chol (p=0.004), small TRL-Chol (p=0.004) and small TRL-RP (p=0.001) than subjects with the -1131TT genotype. The modifications observed in postprandial lipoprotein metabolism in subjects with the apoA-V -1131T>C polymorphism could be involved in the increased fasting plasma TG concentrations previously described in carriers of the C allele.

The Mediterranean and CHO diets decrease VCAM-1 and E-selectin expression induced by modified low-density lipoprotein in HUVECs.

BACKGROUND AND AIM: The oxidative modifications of low-density lipoprotein (LDL) are crucial for the atherosclerosis process. The aim of this study was to determine if the minimally modified LDL, obtained after the ingestion of three different diets, produce differential effects on the vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression in human umbilical endothelial cells (HUVECs). METHODS AND RESULTS: Twenty healthy young males were exposed to three dietary periods. Each period lasted four weeks. During the first period, all subjects consumed a saturated fat (SFA) enriched diet (38% fat, 20% SFA). The second and third dietary periods were administered following a randomized crossover design: a low fat high carbohydrates diet (CHO diet) and a Mediterranean diet. LDL particles, isolated during each dietary period, were oxidized by exposure to UV light and incubated for 48 h with HUVEC. Thereafter, 100 U/mL of TNF-alpha was added and incubation continued for 6 h. Cellular ELISA determined adhesion molecules expression. Lag time, propagation rate and total amounts of formed conjugated dienes were calculated in LDL incubated with 10mumol/L Cu(2+). When compared to the SFA diet, LDL isolated from the Mediterranean and CHO diets induced a lower expression of VCAM-1 and E-selectin in HUVECS (P<0.007). There were no differences between both lipid lowering diets. However, lag time of LDL from the Mediterranean diet was higher than with the CHO diet (P<0.042). This parameter was inversely correlated with E-selectin expression (r=-0.497; P<0.04). CONCLUSION: Our results suggest that both the Mediterranean and CHO diets may decrease the pro-inflammatory environment induced by modified LDL in endothelial cells.

[Level of knowledge and action on lipaemia among Spanish primary and specialist care doctors. Press cholesterol study]. / Nivel de conocimiento y actuación sobre dislipidemias de los médicos de atención primaria y especializada españoles. Estudio Colesterol Press.

OBJECTIVES: To find the level of knowledge, the guidelines for action and the monitoring of lipaemia by Spanish primary care and specialist doctors. DESIGN AND INTERVENTION: A self-defined questionnaire of 12 items was designed. Data on the population treated and the subjective evaluation of objectives, and on the management and monitoring of lipid parameters were filled in. SETTING AND PARTICIPANTS: A total of 1998 doctors from the whole of Spain took part; 68.8% of the doctors interviewed worked in primary health care and 30.2% in specialist centres or hospitals. RESULTS: A 91% of the doctors said they followed international consensus on monitoring lipaemia. The most commonly used objective therapeutic parameter for treating lipaemia was LDL-cholesterol (83%), followed by total cholesterol (62%), HDL-cholesterol (56%) and triglycerides (51%). If the patient's lipaemia was well controlled, then 21.8% of doctors reduced the doses of lipid-lowerers. In general terms, no great differences were appreciated between the criteria followed by PC and by specialist doctors. CONCLUSIONS: The criteria for action on lipaemia could be improved. There are no important differences of view or action in clinical and therapeutic criteria for Lipaemia cases between PC and specialist doctors.

A polymorphism exon 1 variant at the locus of the scavenger receptor class B type I (SCARB1) gene is associated with differences in insulin sensitivity in healthy people during the consumption of an olive oil-rich diet.

UNLABELLED: Scavenger receptor class B type I (SCARB1) was described as the first high-density lipoprotein receptor. Increasing evidence indicates that SCARB1 plays additional roles particularly in type 2 diabetes mellitus. Our aim was to determine whether the presence of an exon 1 (G-->A) polymorphism at the SCARB1 gene modifies the insulin sensitivity to dietary fat. METHODS: We studied 59 healthy volunteers (30 men and 29 women, 42 G/G homozygous and 17 G/A heterozygous). Subjects consumed three diets for 4 wk each: a saturated fatty acid (SFA)-rich diet (38% fat, 20% SFA), followed by a carbohydrate (CHO)-rich diet (30% fat, 55% CHO) or a monounsaturated fatty acid (MUFA)-rich diet (38% fat, 22% MUFA) after a randomized crossover design. For each diet, we investigated peripheral insulin sensitivity with the insulin suppression test. RESULTS: Steady-state plasma glucose after the MUFA diet was lower in G/A compared with G/G subjects (P = 0.030). This effect was not observed after CHO and SFA diets (P = 0.177 and 0.957, respectively). Plasma nonesterified free fatty acid values were lower in subjects carrying the A allele for all the diet periods. CONCLUSIONS: Our findings show that carriers of the G/A genotype have significant increases in insulin sensitivity after a MUFA-rich diet compared with G/G individuals.

The Ala54Thr polymorphism of the fatty acid-binding protein 2 gene is associated with a change in insulin sensitivity after a change in the type of dietary fat.

BACKGROUND: Insulin resistance, a condition associated with type 2 diabetes, results from the interaction of environmental and genetic factors. OBJECTIVE: We examined the influence of the intestinal fatty acid-binding protein 2 (FABP2) Ala54Thr polymorphism on insulin sensitivity. DESIGN: Fifty-nine healthy young subjects (28 were Ala54/Ala54, 27 were Ala54/Thr54, and 4 were Thr54/Thr54) completed 3 diets, each of which lasted 4 wk. The first diet, which all subjects consumed, was a high-saturated fatty acid (SFA) diet (38% of energy as fat and 20% of energy as SFAs). The second and third diets were administered according to a randomized crossover design, and they consisted of a low-fat and high-carbohydrate diet (CHO diet; 28% of energy from fat and <10% of energy from SFAs) and a high-monounsaturated fatty acid (MUFA) diet (called the Mediterranean diet; 38% of energy from fat and 22% of energy from MUFAs). All food and drinks were prepared and provided in the research kitchen. We determined in vivo insulin resistance by using the insulin suppression test with somatostatin. RESULTS: Steady state plasma glucose concentrations were significantly higher in Ala54Thr subjects after the SFA diet than after the CHO diet or the Mediterranean diet. The plasma free fatty acid concentrations in these subjects were significantly lower after the CHO and Mediterranean diets than after the SFA diet. However, no significant differences between the 3 diets were observed in the Ala54 allele homozygotes. CONCLUSION: Insulin sensitivity decreased in subjects with the Thr54 allele of the FABP2 polymorphism when SFAs were replaced by MUFAs and carbohydrates.

The -514 C/T polymorphism in the hepatic lipase gene promoter is associated with insulin sensitivity in a healthy young population.

Impaired insulin action has been associated with diabetes, dyslipidemia and atherosclerotic vascular disease. The expression of insulin resistance results from the interaction of environmental and genetic factors. Human hepatic lipase (HL) is a lipolytic enzyme that plays a role in the metabolism of several lipoproteins, while insulin up-regulates the activity of HL via insulin-responsive elements in the HL promoter. We have examined the influence of -514 C/T polymorphism in the hepatic lipase gene promoter on insulin sensitivity in 59 healthy young subjects (30 males and 29 females). The volunteers were subjected to three dietary periods, each lasting four weeks. During the first period all subjects consumed a saturated fat (SFA)-enriched diet with 38% as fat (20% SFA, 12% monounsaturated fatty acids (MUFA) and 6% polyunsaturated fatty acids (PUFA)). In the second and third dietary periods, a randomized crossover design was used, consisting of a low fat, high carbohydrate diet (CHO diet) (< 10% SFA, 12% MUFA and 6% PUFA) and a high-MUFA, or Mediterranean diet, with < 10% SFA, 22% MUFA and 6% PUFA. We determined the in vivo insulin resistance using the insulin suppression test with somatostatin. Steady-state plasma glucose (SSPG) concentrations (a measure of insulin sensitivity) were significantly higher in men carriers of the -514T allele after the consumption of the SFA diet than after the CHO diet and the Mediterranean diet. This effect was not observed in women. Moreover, there were no significant differences in insulin sensitivity after the three diets in men and women with the CC genotype. In summary, our results show an improvement in insulin sensitivity in men with the -514T allele of the HL promoter polymorphism, when MUFA and carbohydrates are consumed instead of SFA fat.

[Effect of the Mediterranean diet on fasting concentrations of activated factor VII in healthy persons]. / Efecto de la dieta mediterránea en los valores plasmáticos de factor VII activado en personas sanas.

INTRODUCTION AND OBJECTIVES: Many clinical and epidemiologic studies suggest that activated factor VII may be involved in the pathogenesis of coronary heart disease. Our objective was to determine the effect of a Mediterranean diet on plasma levels of activated factor VII in comparison to a low-fat diet and a diet rich in saturated fat. PATIENTS AND METHOD: The study population comprised 16 healthy normolipemic men who consumed 3 different diets in consecutive 28-day periods. The first diet was rich in saturated fat (38% calories as fat, 20% saturated fat), the second was a low-fat, high-carbohydrate diet (28% calories as fat, 10% saturated fat), and the third was enriched in monounsaturated fatty acids (38% calories as fat, 22% monounsaturated fat). At the end of each period, plasma concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, total triglycerides, apolipoprotein A-I, apolipoprotein B, and glucose were measured. Activated factor VII was determined with a coagulation assay. RESULTS: The diet rich in saturated fat was associated with a significant increase in total cholesterol, LDL cholesterol, apolipoprotein AI, and apolipoprotein B in comparison to the other 2 diets. There were no significant differences between the carbohydrate-rich diet and the Mediterranean diet in any of the lipid parameters. The Mediterranean diet decreased plasma levels of factor VIIa in comparison to the diet rich in saturated fat (34.6+/-15.3 mU/mL vs 101.5+/-19.2 mU/mL; P<.05). CONCLUSIONS: In comparison to the diet rich in saturated fat or the high-carbohydrates diet, the Mediterranean diet decreased plasma concentrations of activated factor VII in healthy young men. This phenomenon may constitute another protective mechanism of the Mediterranean diet in reducing cardiovascular risk.

The influence of lipoprotein lipase gene variation on postprandial lipoprotein metabolism.

Lipoprotein lipase (LPL) is one of the key enzymes in the metabolism of triacylglycerol-rich lipoproteins (TRL). We evaluated whether the association of LPL HindIII (H1/H2) and Serine447-Stop (S447X) polymorphisms may explain the interindividual variability observed during postprandial lipemia. Fifty-one healthy male volunteers (26 with the H2S447 genotype, 15 with the H1X447 genotype, and 10 with the H1S447 genotype) were subjected to a vitamin A-fat load test consisting of 1 g fat/kg body weight and 60,000 IU vitamin A. Blood was drawn every hour until the 6th hour and every 2 h and 30 min until the 11th hour. Data revealed that subjects that are homozygous for the H2 allele (H2H2) showed a higher postprandial response for small TRL, retinyl palmitate (RP), large TRL-RP, large TRL-B48, and small TRL-B48 levels. Furthermore, in the case of the S447X polymorphism, 447Ter carriers had a lower postprandial response for small TRL-RP, large TRL-B48, and small TRL-RP. Subjects with the LPL H2S447 genotype had higher plasma triacylglycerol, large TRL-triacylglycerol, large TRL-RP, small TRL-RP, and large TRL-B48 (P < 0.037) than H1X447 subjects. The modifications observed in postprandial lipoprotein metabolism in young normolipemic males with LPL polymorphism could be involved in the lower risk of coronary artery disease associated with the H1X447 genotype.

Apolipoprotein E gene promoter -219G->T polymorphism increases LDL-cholesterol concentrations and susceptibility to oxidation in response to a diet rich in saturated fat.

BACKGROUND: The apolipoprotein E (APOE) gene promoter polymorphism (-219G-->T) has been associated with increased risk of myocardial infarction, premature coronary artery disease, and decreased plasma apolipoprotein E concentrations. OBJECTIVE: We aimed to determine in healthy subjects whether this polymorphism modifies the susceptibility of LDL to oxidation and the lipid response to the content and quality of dietary fat. DESIGN: Fifty-five healthy men with the APOE3/E3 genotype (7 GG, 38 GT, and 10 TT) completed 3 dietary periods, each lasting 4 wk. The first was a saturated fatty acid (SFA)-rich diet [38% fat-20% SFA and 12% monounsaturated fatty acid (MUFA)-and 47% carbohydrates (CHO)], which was followed by a CHO-rich diet (30% fat-<10% SFA and 12% MUFA-and 55% CHO) or a MUFA-rich diet (38% fat-<10% SFA and 22% MUFA-and 47% CHO) in a randomized crossover design. At the end of each dietary period, LDL oxidation susceptibility, lipids, and lipoproteins were measured. RESULTS: Compared with carriers of the G allele, TT subjects had a significantly (P < 0.05) shorter lag time after the SFA diet. The replacement of the SFA diet by the CHO or MUFA diet induced a greater increase (P < 0.05) in lag time in the TT subjects than in the GG or GT subjects. Carriers of the T allele had higher LDL-cholesterol (P < 0.05) and apolipoprotein B (P < 0.05) plasma concentrations after the SFA diet than did GG subjects. Compared with GG subjects, carriers of the T allele had a significantly (P < 0.05) greater decrease in LDL cholesterol and apolipoprotein B when they changed from the SFA to the CHO diet. CONCLUSION: The -219G-->T polymorphism may partially explain differences in individual responses to diet.

Effects of the human apolipoprotein A-I promoter G-A mutation on postprandial lipoprotein metabolism.

BACKGROUND: There is considerable interindividual variability in the postprandial lipid response to a fat-rich meal, and genetic factors have been considered to account for some of these effects. We previously showed that the G-A mutation 5' to the apolipoprotein (apo) A-I gene was significantly associated with the LDL-cholesterol response to diet. OBJECTIVE: We evaluated whether this effect is mediated by mechanisms involving postprandial lipoprotein metabolism. DESIGN: Twenty-eight G/G and 23 G/A healthy male subjects, homozygotes for the apo E3 allele, were subjected to a vitamin A fat-loading test. Blood was drawn at time 0 and every hour for 11 h. RESULTS: There was a significant postprandial decrease in plasma cholesterol, LDL cholesterol, and apo B in G/G subjects but not in G/A subjects. A greater postprandial response in large triacylglycerol-rich lipoproteins (TRLs) and a smaller postprandial response in large TRL apo A-IV was observed in G/A than in G/G subjects. Retinyl palmitate in large and small TRL concentrations was similar for both genotypes. No significant genotype effects were detected for triacylglycerol concentrations in plasma, small TRL fraction, and apo A-I and HDL-cholesterol concentrations. CONCLUSION: Our data suggest that the G-A mutation affects the LDL-cholesterol response to diet by mechanisms involving postprandial lipoprotein cholesterol metabolism.

Butter and walnuts, but not olive oil, elicit postprandial activation of nuclear transcription factor kappaB in peripheral blood mononuclear cells from healthy men.

BACKGROUND: Nuclear transcription factor kappaB (NF-kappaB) plays an important role in atherosclerosis by modulating gene expression. Postprandial lipemia has been correlated with an increase in NF-kappaB activation in vascular cells and it is associated with an increase in postprandial triacylglycerol-rich lipoproteins, which are involved in the development of atherosclerotic plaque. OBJECTIVE: The objective of this study was to determine the effect of the intakes of 3 different foods with different fat compositions on the postprandial activation of monocyte NF-kappaB. DESIGN: Eight healthy men followed a 4-wk baseline diet and then consumed 3 fat-load meals consisting of 1 g fat/kg body wt (65% fat) according to a randomized crossover design. Each meal had a different fatty acid composition, and the consumption of each meal was separated by 1 wk. The compositions of the 3 test meals were as follows: olive oil meal [22% saturated fatty acids (SFAs), 38% monounsaturated fatty acids (MUFAs), 4% polyunsaturated fatty acids (PUFAs), and 0.7% alpha-linolenic acid], butter meal (38% SFAs, 22% MUFAs, 4% PUFAs, and 0.7% alpha-linolenic acid), and walnut meal (20% SFAs, 24% MUFAs, 16% PUFAs, and 4% alpha-linolenic acid). RESULTS: Ingestion of the olive oil meal did not elicit NF-kappaB activation compared with ingestion of either the butter meal at 3 h (P <0.05) or the walnut meal at 9 h (P <0.05). There was no significant difference in the postprandial triacylglycerol response between the 3 meals. CONCLUSIONS: Consumption of an olive oil-enriched meal does not activate NF-kappaB in monocytes as do butter and walnut-enriched meals. This effect could enhance the cardioprotective effect of olive oil-enriched diets.

Polymorphism exon 1 variant at the locus of the scavenger receptor class B type I gene: influence on plasma LDL cholesterol in healthy subjects during the consumption of diets with different fat contents.

BACKGROUND: The association between polymorphisms in the scavenger receptor class B type I (SRB-I) gene and variations in basal plasma concentrations of cholesterol in humans has recently been described. OBJECTIVE: The objective of the study was to determine whether the exon 1 variant (G-->A) at the SRB-I gene is associated with the lipid response to the content and quality of dietary fat in healthy subjects. DESIGN: We studied 97 healthy volunteers with exon 1 polymorphism [65 homozygous for allele 1 (1/1) and 32 heterozygous for allele 2 (1/2)]. Both groups consumed 3 diets lasting 4 wk each. The first was a saturated fatty acid (SFA)-rich diet (38% fat, 20% SFA), which was followed by a carbohydrate (Cho)-rich diet (30% fat, < 10% SFA, 55% carbohydrate) or a monounsaturated fatty acid (MUFA), olive oil-rich diet (38% fat, 22% MUFA) according to a randomized crossover design. At the end of each dietary period, plasma concentrations of triacylglycerol and of total, LDL, and HDL cholesterol were measured. RESULTS: Carriers of the 1/2 genotype had a trend toward higher concentrations of LDL cholesterol (P < 0.11) after the SFA-rich diet than did those who were homozygous for 1/1. Carriers of the mutation showed a significantly greater (P = 0.007) decrease in LDL-cholesterol concentrations (-23%) in changing from an SFA-rich diet to a Cho-rich diet than did noncarriers of the mutation (-16%). CONCLUSION: Carriers of the minority allele, 1/2, are more susceptible to the presence of SFA in the diet because of a greater increase in LDL cholesterol.

Influence of the -514C/T polymorphism in the promoter of the hepatic lipase gene on postprandial lipoprotein metabolism.

The -514C/T polymorphism located in the promoter region of the hepatic lipase gene mediates changes in the plasma levels of the enzyme. The aim of this study was to determine whether the presence of this polymorphism modifies the postprandial clearance of lipoproteins of intestinal origin. 51 normolipemic volunteers, homozygotes for the allele E3 of the apo E were selected (26 homozygotes for the C allele and 25 carriers of the T allele in both homozygote and heterozygote form). The subjects underwent a Vitamin A fat-loading test. Blood was drawn every hour until the 6th hour and every 2 h and 30 min until the 11th hour to determine cholesterol and plasma triglycerides as well as cholesterol, triglycerides (TG) and retinyl palmitate in triacylglycerol-rich lipoproteins (chylomicrons and chylomicron remnants). Carriers of the T allele showed significantly lower postprandial levels of apolipoprotein B (P < 0.01), total TG in plasma (P < 0.05), small TRL-TG (P < 0.04), large TRL-TG (P < 0.04) and small TRL-cholesterol (P < 0.04) when compared to subjects homozygous for the C allele. Our data suggest that the T allele of the -514C/T polymorphism in the promoter region of the hepatic lipase gene is associated with a lower postprandial lipemic response.