Henar Ortega

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.

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 ε3 allele homozygosity as reference, in boys with birth weights in the low tertile the overall lowering effect of the ε2 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 ε2, which may explain the fact that the decrease in TC, LDL-C and apo B associated with the ε2 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.

Nandrolone decanoate reduces serum lipoprotein(a) concentrations in hemodialysis patients.

We have studied the changes in the lipid profile of 14 chronic hemodialysis patients receiving a 6-month cycle of nandrolone decanoate as treatment for anemia. Nandrolone decanoate was administered in a weekly intramuscular dose of 200 mg and resulted in an increase in the hemoglobin concentration (baseline, 7.9 +/- 0.9 g/dL; month 6, 10.8 +/- 1.7 g/dL; P < 0.001, ANOVA) and also produced relevant modifications in the lipid concentrations. The most significant finding was a decrease in the concentration of lipoprotein(a) [Lp(a)]: baseline, 19.8 mg/dL (median), month 2, 10.6 mg/dL; month 4, 8.7 mg/dL; and month 6, 7.1 mg/dL (P < 0.001, Friedman). Other lipid changes induced by nandrolone decanoate were an increase in the concentrations of apolipoprotein B (P < 0.02, ANOVA) and triglyceride (P = NS, ANOVA) and a decrease of high-density lipoprotein (HDL) cholesterol (P < 0.001, ANOVA) and apolipoprotein A-I (P = NS, ANOVA). The decrease in HDL cholesterol was at the expense of the HDL2 cholesterol subfraction, whereas HDL3 remained unchanged. These lipid modifications were reversible; 4 months after nandrolone decanoate withdrawal, the lipid concentrations were similar to the basal values. The changes in Lp(a) levels did not correlate with those of hemoglobin or the other lipid parameters, suggesting that the underlying mechanisms are unrelated. Our findings could be clinically relevant if confirmed by further studies.

Effects of normalization of GH hypersecretion on lipoprotein(a) and other lipoprotein serum levels in acromegaly.

Lipoprotein(a) has been recognized as an important risk factor for cardiovascular disease. Lipoprotein(a) has been found to be elevated in sera of acromegalic patients, possibly contributing to the increased incidence of coronary heart disease found in these patients. In the present study we sought to determine the effects of GH hormonal status on lipoprotein(a) and other lipid parameters, including lipoprotein lipase (LPL) activity.

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.

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

Abstract 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 1266 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. Clin Chem Lab Med 2008;46:809–13.

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.