Fat intake influences the effect of the hepatic lipase C-514T polymorphism on HDL-cholesterol levels in children.

Polymorphisms in the hepatic lipase gene have been associated with variability in plasma HDL-C concentrations, but contradictory results have been reported regarding the effect of diet on this association in adults. In our study, we examined whether dietary fat intake modified the association between lipid levels and the C-514T polymorphism in the hepatic lipase gene (LIPC C-514T) in prepubescent children. The LIPC C-514T polymorphism was determined by PCR and restriction analysis in 1260 healthy school children, aged 6-8. Information on the children's nutrient intake was obtained by means of a validated food frequency questionnaire. We found that regardless of gender, carriers of the minor allele had significantly higher apo A-I levels compared to noncarrier subjects. The effect of the polymorphism, however, was modified by dietary fat intake. In boys, the presence of the LIPC C-514T polymorphism was associated with significantly higher HDL-C among children within the highest tertiles of total, saturated, monounsaturated, or polyunsaturated fat intake. Apo A-I levels were significantly higher in carriers of the LIPC C-514T polymorphism, but only among boys who consumed high total as well as monounsaturated fat and among girls who consumed high total, saturated, monounsaturated, and polyunsaturated fat. Our data show that dietary fat intake modifies the effect of the LIPC C-514T polymorphism on plasma HDL-C and apo A-I levels in prepubescent children, being associated with higher levels of HDL-C and apo A-I only when fat intake is high. This significant gene-nutrient interaction could help to explain inter-individual variations in the plasma lipid response to fat intake.

Maternal and fetal fatty acid profile in normal and intrauterine growth restriction pregnancies with and without preeclampsia.

The aim of this study was to evaluate maternal and fetal lipid profile in intrauterine growth restriction (IUGR) pregnancies with and without preeclampsia (PE). Thirteen normal pregnancies studied during the third trimester (control M) and 29 at elective cesarean section (control CS) were compared with 18 pregnancies complicated by IUGR (IUGR only) and with seven pregnancies complicated by both IUGR and PE (IUGR-PE). Total plasma fatty acids, triglycerides, cholesterol, and nonesterified fatty acids (NEFA) were determined in maternal and fetal plasma. Nutritional intake was analyzed. IUGR only mothers had lower percentage of linoleic acid (LA) and higher arachidonic acid (AA) than controls, partly explained by higher AA dietary intake. Higher levels of NEFA were observed both in IUGR only and in IUGR-PE mothers whereas triglyceride levels were increased in IUGR-PE mothers only. In IUGR-PE fetuses, LA and AA were significantly decreased, whereas triglyceride and NEFA concentrations were significantly increased compared with normal fetuses. In conclusion, IUGR only is associated with altered fatty acids profile not completely accounted by dietary changes. We hypothesize that the differences observed in IUGR with PE for triglycerides and other lipids could be related to a difference in maternal phenotype.

Activation of phospholipase A2 is associated with generation of placental lipid signals and fetal obesity.

CONTEXT: Obesity and diabetes during pregnancy are associated with increased insulin resistance and higher neonatal adiposity. In turn, insulin resistance triggers inflammatory pathways with accumulation of placental cytokines. OBJECTIVE: To determine placental signals that translate into development of excess adipose tissue, we investigated the role of phospholipases A2 (PLA2) as targets of inflammatory mediators. SETTING: The study was conducted at Case Western Reserve University, Department of Reproductive Biology. SUBJECTS: Volunteers gave informed written consent in accordance with the Institutional Review Board guidelines. Placenta and cord blood samples were obtained at the time of elective cesarean section in 15 term pregnancies. INTERVENTION: Neonatal anthropometric measurements were performed within 48 h of delivery. Placentas were grouped based on neonatal percentage body fat as obese (body fat > or = 16%) and lean control (body fat < or = 8%). MAIN OUTCOME MEASURES: The primary outcomes were placenta PLA2 expression and fatty acid concentration. RESULTS: Expression of PLA2G2A and PLA2G5, the main placenta phospholipases, was greater (P < 0.05) in placenta of obese compared with control neonates and was associated with increased 20:3 and 20:5 omega-3 polyunsaturated fatty acids. TNF-alpha and leptin content was increased 3-fold in placenta of obese neonates. TNF-alpha and leptin both induced a time-dependent activation of PLA2G2 and PLA2G5 in placental cells. CONCLUSION: Accumulation of omega-3 fatty acids through secretory PLA2 activation is associated with high neonatal adiposity. We propose that the generation of placental lipid mediators through TNF-alpha and leptin stimulation represents a key mechanism to favor excess fetal fat accretion.

Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinflammatory effects in both hemodialysis patients and healthy subjects.

BACKGROUND: Patients treated with hemodialysis frequently experience cardiovascular complications attributed, among other causes, to dyslipidemia, increased oxidative stress, and inflammation. OBJECTIVE: The aim of the study was to study the effects of dietary supplementation with concentrated red grape juice (RGJ), a source of polyphenols, on lipoprotein profile, antioxidant capacity, LDL oxidation, and inflammatory biomarkers. DESIGN: Twenty-six patients receiving hemodialysis and 15 healthy subjects were instructed to drink 100 mL RGJ/d for 14 d. Blood was drawn at baseline, twice during RGJ supplementation, and twice during the 6-mo follow-up period. As a control, 12 other randomly recruited hemodialysis patients not receiving RGJ were studied. Lipids, apolipoproteins, oxidized LDL, and antioxidant vitamins were measured in plasma. The bioavailability of RGJ polyphenols was assessed in healthy subjects. RESULTS: The maximum plasma concentration of quercetin was achieved 3 h after RGJ ingestion, which indicates that supplement-derived polyphenols are rapidly absorbed. In both healthy subjects and hemodialysis patients, RGJ consumption increased the antioxidant capacity of plasma without affecting concentrations of uric acid or ascorbic acid; reduced the concentration of oxidized LDL; and increased the concentration of cholesterol-standardized alpha-tocopherol. RGJ supplementation also caused a significant decrease in LDL-cholesterol and apolipoprotein B-100 concentrations, while increasing the concentrations of HDL cholesterol and apolipoprotein A-I. In a further study in hemodialysis patients, RGJ supplementation for 3 wk significantly reduced plasma monocyte chemoattractant protein 1, an inflammatory biomarker associated with cardiovascular disease risk. CONCLUSION: Dietary supplementation with concentrated RGJ improves the lipoprotein profile, reduces plasma concentrations of inflammatory biomarkers and oxidized LDL, and may favor a reduction in cardiovascular disease risk.

Influence of apolipoprotein E genotype on fat-soluble plasma antioxidants in Spanish children.

BACKGROUND: Apolipoprotein (apo) E is a major determinant of plasma lipid concentrations, which in turn influence the plasma concentrations of various fat-soluble vitamins. OBJECTIVE: We aimed to analyze the effect of APOE genotype on fat-soluble antioxidant concentrations in children. DESIGN: A total of 926 healthy boys and girls aged 6-8 y were selected from 4 cities in Spain. APOE genotyping was carried out, and plasma concentrations of lipids, apolipoproteins, and lipid-soluble antioxidants were measured. RESULTS: Plasma lipid concentrations were strongly influenced by APOE genotype. The mean plasma concentration of alpha-tocopherol was 21.3 micromol/L, which is one of the highest values ever reported for a population of children. Although plasma concentrations of alpha-tocopherol, gamma-tocopherol, lycopene, and alpha-carotene varied significantly between subjects with different APOE genotypes, most of these differences disappeared after adjustment for lipoprotein-related covariates. Nevertheless, tocopherol concentrations remained elevated in individuals with the E2/2 genotype. Multivariate regression analysis showed interactions of APOE genotype with triacylglycerol and apo B in determining alpha-tocopherol concentrations. When subjects were stratified according to major apo E groups, apo B appeared to be the most important predictor of alpha-tocopherol concentrations in all groups, whereas triacylglycerol was identified only in carriers of the E2 allele. CONCLUSIONS: The association between APOE genotype and lipophilic antioxidant concentrations is dependent mainly on the effect of the polymorphism on lipoprotein concentrations. However, triacylglycerol plays a role in determining the variability of alpha-tocopherol concentrations in E2 carriers only. This suggests that the alpha-tocopherol content in each lipoprotein class varies according to APOE genotype.

Effects of dehydroepiandrosterone-sulfate on the Apo E genotype influence on plasma lipid levels in prepubertal children.

Gender differences in the apolipoprotein (apo) E genotype effect on plasma lipid levels reported in adults have also been found in pre-pubertal children. In adults, the difference seems to be due to the influence of sexual hormones. The reason why this difference exits between pre-pubertal girls and boys, for whom those sexual hormones are not different, is unclear. However, there is an important difference in Dehydroepiandrosterone-sulfate (DHEA-S) levels between pre-pubertal boys and girls. To evaluate the influence of DHEA-S on apo E genetic determinants of plasma lipids levels in pre-pubertal children we measured plasma DHEA-S in 1045 healthy children (534 males and 511 females) 6 to 8 years old in which a different apoE influence on lipid levels had been reported between girls and boys. Our observations demonstrate that the extent of the lipid increasing or decreasing effects associated with each allele were modulated by DHEA-S. DHEA-S increases the hypolipemic effect of the epsilon2 allele and decreases the hyperlipemic effect of the epsilon4 allele. In conclusion, the interaction of apo E genotype and DHEA-S may represent a critical determinant of TC, LDL-C and apo B levels in children at the prepuberal age.

Liquid chromatographic method for the simultaneous determination of different lipid-soluble antioxidants in human plasma and low-density lipoproteins.

We describe a reverse phase HPLC method, employing a simple methanol:water gradient as mobile phase, for the determination of several lipophilic antioxidants, such as retinol, gamma-tocopherol, alpha-tocopherol, lycopene, alpha-carotene and beta-carotene among others, using UV detection. Additionally, this method allows the simultaneous separation of probucol, an hypocholesterolemic drug with antioxidant properties. Retinol acetate and alpha-tocopherol acetate were added to samples as internal standards. A NovaPack ODS C18, 150 x 3.9 mm, 0.4 microm column was used and the flow rate was set constant at 1m/min, which allowed the separation of all the desired antioxidants in a total run time of 35 min. A photodiode array detector was used because of its advantages to study the purity of the peaks, however, any programmable multiwavelength UV/VIS detector could be employed given the good resolution of the peaks. The analytical recoveries of the studied compounds were > 96% and the detection limits were: retinol 0.050 microg/ml, gamma-tocopherol 0.137 microg/ml, alpha-tocopherol 0.906 microg/ml, lycopene 0.022 microg/ml, alpha-carotene 0.008 microg/ml, beta-carotene 0.015 microg/ml and probucol 1.503 microg/ml. The intra- and inter-assay coefficients of variation were calculated by using two human plasma samples with different levels of lipophilic antioxidants. The simplicity, rapidity and economy, make this method suitable for the routine measurement of plasma and low-density lipoproteins antioxidants, and may also be used in large scale epidemiological studies. The method has been used to measure antioxidants in samples from patients undergoing treatment with probucol, showing there is a good correlation between the probucol content in LDL and that in total plasma.

[Metabolic factors in school children population associated with adult cardiovascular mortality. Four provinces' study]. / Factores metabólicos en la población escolar asociados a mortalidad cardiovascular en los adultos. Estudio Cuatro Provincias.

BACKGROUND: Environmental factors in early stages of life may contribute to adult cardiovascular disease. We have examined certain anthropometric and biochemical variables in children aged 6-7 years from four Spanish provinces with high differences in mortality due to ischemic heart disease (IHD). PATIENTS AND METHOD: We performed a cross-sectional survey of 1,255 children (50.3% males) attending schools in Cádiz and Murcia provinces with a relatively high IHD mortality and Madrid and Orense provinces with a relatively low IHD mortality. Weight, body mass index (BMI) and prevalence of obesity were analyzed, and plasma glucose and lipid levels were measured by standardized methods. RESULTS: Compared with children in the two low-IHD-mortality provinces, those in the two high-IHD-mortality provinces had greater weight (p < 0.05) and BMI (p < 0.01) and higher prevalence of obesity (p < 0.01). Moreover, they had significantly higher (p < 0.01) plasma glucose, triglyceride and apo A-I levels. CONCLUSIONS: The higher prevalence of overweight and obesity, along with higher plasma glucose and triglyceride levels, in provinces with high coronary artery disease mortality indicates that children from these provinces are metabolically different from those in provinces with low coronary artery disease mortality. These alterations may thus contribute to the different IHD mortality in adulthood.

Plasma non-esterified fatty acid levels in children and their relationship with sex steroids.

OBJECTIVE: Puberty is associated with decreased insulin sensitivity. Sexual hormones have been related with the onset of insulin resistance, but their relationship with non-esterified fatty acids (NEFA) remains unexplored. The aim of this study was to evaluate circulating NEFA levels in population-based samples of prepubertal children and adolescents and to analyze the association of NEFA with obesity, insulin resistance, and sexual hormones in adolescents. EXPERIMENTAL: The studied population included 854 randomly selected 6-8-year-old children and 822 children aged 12-16years. NEFA levels were determined using a commercial kit. Testosterone and estradiol levels were determined by RIA, and insulin and sex hormone binding protein by IRMA. HOMA was calculated as an indicator of insulin resistance. RESULTS: NEFA levels were lower in adolescents than in 6-8-year-old children, and decreased progressively with age between 12-year-olds and 16-year-olds. No significant differences in NEFA levels were observed between obese and non-obese adolescents. NEFA were not correlated with insulin or HOMA in 12-16-year-old girls, and appear negatively correlated with these variables in boys. Insulin and HOMA were negatively correlated with SHBG levels in both sexes adjusting by age but NEFA levels were not. CONCLUSIONS: NEFA levels decrease with age in adolescents and are not significantly increased in obese children, supporting the fact that the decreased insulin sensitivity at this age is not affecting NEFA metabolism. Although SHBG is related to insulin and HOMA independently of age in both sexes, SHBG levels are not associated with NEFA.

High-density lipoprotein cholesterol and paraoxonase 1 (PON1) genetics and serum PON1 activity in prepubertal children in Spain.

BACKGROUND: Oxidative stress plays an important role in atherosclerosis. Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme that inhibits low-density lipoprotein (LDL) oxidation and may play a protective role against coronary heart disease. The aim of this study was to analyze the relationship between HDL-cholesterol (HDL-C) and PON1 in a Spanish prepubertal population with high plasma HDL-C levels. METHODS: The study population included 1,266 children between the ages of 6 and 8 years. Serum PON1 activity was measured by the hydrolysis of paraoxon. PON1 192Q/R and PON1 55L/M polymorphisms were analyzed by PCR and restriction analysis. RESULTS: The prevalence of the less common PON1 192R and PON 55M alleles in this population was 30% and 38%, respectively. No significant correlations between serum PON1 activity and lipid profile were observed. Multiple linear regression analysis showed that the PON1 192Q/R polymorphism accounts for 69% of PON1 activity in the children in the study, with the PON1 55L/M polymorphism accounting for an additional 5% of this variation in boys, and for an additional 3% together with HDL-C concentration in girls. CONCLUSIONS: PON1 192Q/R polymorphism is the main determinant of PON1 activity in the prepubertal population in this study, accounting for around 70% of serum PON1 activity. HDL-C concentration has a small contribution to serum PON1 activity in girls.

Obesity in Spanish schoolchildren: relationship with lipid profile and insulin resistance.

This article reports cross-sectional data from a total of 1048 children, 6 to 8 years of age, categorized by presence or absence of obesity, who participated in a voluntary survey of cardiovascular risk factors in Spain over the period of 1998 to 2000, to establish the relationship between obesity and its metabolic consequences at this age. The prevalence of obesity and overweight were 9.4% and 15.7%, respectively, in boys and 10.5% and 18.0%, respectively, in girls. We observed that, in both sexes, obese children had higher triglycerides and lower high-density lipoprotein-cholesterol levels than non-obese children. No differences were found in plasma glucose or low-density lipoprotein-cholesterol levels between normal and obese children. However, we observed that insulin levels and the homeostasis model assessment for insulin resistance were significantly (p<0.001) higher in obese children of both sexes but that free fatty acid levels were lower in obese children than in nonobese children, with a statistical significance in girls (0.72+/-0.30 vs. 0.61+/-0.16 mEq/liter). In summary, our survey found some metabolic consequences of obesity similar to those found in adults (elevated triglycerides, insulin, and the homeostasis model assessment for insulin resistance, and lower high-density lipoprotein-cholesterol). However, other features (glucose, total cholesterol, low-density lipoprotein-cholesterol, and free fatty acid levels) were found to behave differently, indicating that the association of obesity with risk factors seems to change as the children age and may depend on the chronology of sexual maturation.

Influence of birth weight on the apo E genetic determinants of plasma lipid levels in children.

To evaluate the influence of birth weight on apolipoprotein (apo) E genetic determinants of plasma lipids levels in prepubertal children we studied 933 healthy children (491 males and 442 females) 6 to 8 years old (mean age of 6.7 y), whose weight was recorded at birth. Plasma lipid and apolipoprotein concentrations and apo E genotypes were determined. We observed a greater effect of the apo E polymorphism on total cholesterol (TC), LDL-cholesterol (LDL-C) and especially apo B levels in children with birth weight in the lower tertile compared with those with birth weights in higher tertiles. Taking the epsilon3 allele homozygosity as reference, in boys with birth weights in the low tertile the overall lowering effect of the epsilon2 allele on TC, LDL-C and apo B was greater (10.5% (p < 0.01), 20.2% (p < 0.01) and 18.8% (p < 0.01), respectively) than in those in the highest tertile (5.6% on TC, 10.3% on LDL-C and 12.6% (p < 0.01) on apo B). A similar trend in this effect between tertiles of birth weight was also observed in girls. For both sexes, linear regression analysis demonstrates a positive and significant interaction between birth weight and epsilon2, which may explain the fact that the decrease in TC, LDL-C and apo B associated with the epsilon2 allele is more marked the lower the birth weight. Taking into account the prevalence of apo E polymorphism, and that appears to be the main genetic factor affecting plasma lipids, the interaction of apo E genotype and birth weight could be an important determinant of TC, LDL-C and apo B levels, and, as a consequence, of atherosclerosis.

Factores metabólicos en la población escolar asociados a mortalidad cardiovascular en los adultos. Estudio Cuatro Provincias / Metabolic factors in school children population associated with adult cardiovascular mortality. Four Provinces Study

FUNDAMENTO: Existen evidencias sobre la contribución de factores ambientales en etapas tempranas de la vida a la aparición de la enfermedad cardiovascular en la edad adulta. Por ello, en el presente trabajo hemos examinado variables antropométricas y bioquímicas en niños de 6-7 años de cuatro provincias españolas con una gran variación en la mortalidad por cardiopatía isquémica (CI). PACIENTES Y MÉTODO: Estudio transversal en 1.255 niños en edad escolar (50,3 por ciento varones) de Cádiz y Murcia, provincias con alta mortalidad por CI, y de Madrid y Orense, provincias con baja mortalidad por CI, en los que se han analizado peso, índice de masa corporal (IMC) y prevalencia de obesidad, y se han determinado los valores plasmáticos de glucosa y el perfil lipídico mediante métodos estandarizados. RESULTADOS: Los niños de las provincias con mayor mortalidad tienen mayor peso (p < 0,05), IMC (p < 0,01) y prevalencia de obesidad (p < 0,01). Además, presentan valores plasmáticos significativamente más altos (p < 0,01) de glucosa, triglicéridos y apo A-I. CONCLUSIONES: La mayor prevalencia de sobrepeso y obesidad, junto con los elevados valores de glucosa y triglicéridos asociados a las provincias de alta mortalidad, indica que los niños de estas provincias son metabólicamente distintos de los de provincias de baja mortalidad. Estas alteraciones podrían contribuir a la distinta mortalidad cardiovascular en la edad adulta. (AU)