Relationship of NEFA concentrations to RBP4 and to RBP4/retinol in prepubertal children with and without obesity.

BACKGROUND: The regulation of adipose tissue metabolism in early childhood obesity is not well understood. Insulin levels are higher and insulin resistance seems to be present in prepubertal children with obesity but, differing from their behavior in adults with obesity, non-esterified fatty acid (NEFA) concentrations are not increased. Retinol-binding protein (RBP)-4 concentration is associated with obesity and insulin resistance conditions, but the means of this relationship remain unclear, and few studies have taken retinol values into account to evaluate it. OBJECTIVE: To analyze the relationship between RBP4 concentration and lipolytic products in plasma in 141 prepubertal children aged 6 to 8 years, with and without obesity. METHODS: Plasma glucose, insulin, triacylglycerols, NEFA, glycerol, leptin, RBP4, and retinol were analyzed in obese and in their normal-weight counterparts. Homeostatic model assessment, quantitative insulin sensitivity check index, and fasting glucose to insulin ratio were calculated as indicators of insulin resistance. RESULTS: Fasted plasma NEFA concentrations were lower in children with obesity than in their normal weight counterparts, despite leptin, insulin resistance indices, RBP4, retinol, and RBP4/retinol (an index of free-RBP4) being higher. NEFA and glycerol concentrations were inversely correlated with RBP4/retinol in children with obesity but not in those without obesity. In normal weight children, total RBP4 correlated negatively with NEFA and glycerol concentrations and positively with insulin and homeostasis model assessment for insulin resistance. These results indicate that a low saturation of RBP4 with retinol, which implies a higher concentration of free-RBP4, may preserve the antilipolytic function of insulin in adipose tissue in children with obesity. CONCLUSION: Our findings suggest that, in prepubertal children with obesity and insulin resistance, the amount of RBP4/retinol correlates with the antilipolytic response of the adipose tissue to insulin rather than the total RBP4 concentration.

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.

Influence of the interaction between the adiponectin G276T polymorphism and body mass index on lipid levels in healthy children.

Adiponectin is an adipose tissue-specific hormone which is inversely associated with metabolic alterations related to atherosclerosis. Polymorphisms in the adiponectin gene (AdipoQ) have been related to low adiponectin levels as well as several cardiovascular risk factors, but this association remains controversial. In our study we investigated the relationship between the AdipoQ T45G (rs: 2241766) and G276T (rs: 1501299) polymorphisms and adiponectin concentrations, blood pressure, and lipid and insulin levels, in a population-based sample of 12- to 16-year-old children. The study included 815 healthy Spanish children (388 boys and 427 girls). Plasma glucose and lipid levels were determined by standard methods. Insulin concentrations were measured by RIA, and serum adiponectin levels were determined by ELISA. The AdipoQ T45G and AdipoQ G276T polymorphisms were determined by TaqMan(®) allelic discrimination assays. ANOVA or t test allowed for comparison of the studied parameters across genotypes or genotype groups, respectively. A linear regression analysis was performed to examine the independent relationships of the lipid variables with BMI (body mass index), AdipoQ G276T polymorphism and the interaction between the two. When independently comparing the effect of these polymorphisms in normal-weight and overweight children, we observed that overweight boys carriers of the minor allele T had significantly lower TC, LDL-C and apo A-I levels than non-carriers, but these differences were not apparent in normal-weight boys. Furthermore, linear regression analysis demonstrated that interaction between the BMI and the AdipoQ G276T polymorphism is a significant factor explaining the variations of TC and LDL-C levels. To our knowledge, this is the first study to report an association between the AdipoQ G276T polymorphism and lipid levels in overweight boys alone, thereby suggesting that the influence of the AdipoQ polymorphisms on cardiovascular risk factors may be dependent on BMI.

Relationship of adiponectin with metabolic syndrome components in pubertal children.

OBJECTIVE: Adiponectin is an adipose tissue-derived adipocytokine which appears in decreased concentrations in obese patients and in several processes related to cardiovascular disease, such as type 2 diabetes or metabolic syndrome. The aim of this study was to analyze the relationship between adiponectin and components of metabolic syndrome (lipid profile, blood pressure, insulin and insulin resistance) in pubertal Spanish children. METHODS: The population-based sample included 810 healthy children (382 boys and 428 girls) 12-16 years of age. Anthropometric parameters and blood pressure were measured. Lipid levels were determined by standard methods, and insulin and adiponectin concentrations were measured by ELISA. Insulin resistance index was assessed by HOMA-IR. RESULTS: Adiponectin levels were negatively correlated with insulin and HOMA in both boys and girls, and remained significant after adjustment for BMI z-score in girls. After this adjustment, adiponectin maintained a positive correlation with HDL-cholesterol and HDL-phospholipids in both genders, and correlated with triglycerides in girls. Multiple linear regression analysis showed that, after adjustment for BMI z-score, adiponectin accounted for 15.8% of the variation of HDL-cholesterol in girls and for 5% of its variation in boys; meanwhile, it accounted for 15.8% and 12.7% of the variation of HDL-phospholipids in girls and boys, respectively. CONCLUSIONS: Adiponectin levels in 12- to 16-year-old children appear to be more strongly related to better lipid profile and insulin sensitivity in girls than in boys. Our study shows, for the first time to our knowledge, a significant positive correlation between adiponectin and HDL-phospholipids in pubertal children.

The apolipoprotein A5 (APOA5) gene predisposes Caucasian children to elevated triglycerides and vitamin E (Four Provinces Study).

OBJECTIVE: Apolipoprotein A-V plays an important role in lipid metabolism regulation, particularly modulating triglyceride levels, as has been shown by many association studies in adults. The aim of this study was to analyse the effect of APOA5 on lipid profiles and fat-soluble vitamins (due to its strong relationship with triglyceride metabolism) in children. METHODS: We determined polymorphisms -1131T>C and S19W in the APOA5 gene in 964 6-8-year-old participants of the 4P study and analysed the influence of the APOA5 gene on plasma lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides), apolipolipoproteins (apo A-I and apo B) and fat-soluble antioxidant vitamin (α-tocopherol, γ-tocopherol, lycopene, α-carotene, ß-carotene and retinol) levels. RESULTS: The allele frequencies of both polymorphisms were comparable to those described in adult Caucasian populations (0.08 and 0.07 for -1131T>C and S19W, respectively). Boys carrying the -1131C allele have a 12% increase in circulating triglyceride levels (p=0.016) and a 7% decrease in HDL phospholipid levels (p=0.016). Linked to its effect on triglycerides, boys with the -1131C allele also have a 5% increase in plasma α-tocopherol levels (p=0.032). This effect was not observed in female participants. Boys carrying the rare allele for the S19W polymorphism have a 4% increase in circulating cholesterol levels (p=0.045), whereas girls have a 9% increase in circulating triglyceride levels (p=0.029). Linked to its effect on triglycerides, female carriers of the rare allele for S19W also have a 6% increase in α-tocopherol levels (p=0.009). CONCLUSION: In children, the effect of APOA5 gene variants on triglyceride levels is related to gender, and because of the strong relationship between lipid metabolism and fat-soluble antioxidant vitamins, it also involves a significant elevation in α-tocopherol concentrations.

Influence of the leptin G-2548A polymorphism on leptin levels and anthropometric measurements in healthy Spanish adolescents.

Polymorphisms in the leptin gene (LEP) have been associated with leptin levels and obesity in some studies in adults though this link has scarcely been investigated in children. In our study, we examined the relationship of the LEP G-2548A polymorphism with leptin levels, anthropometric variables and body composition in a population-based sample of pubescent children. Our study included 880 healthy schoolchildren (419 males and 461 females), 12-16 years of age. Plasma leptin levels were determined by ELISA. The LEP polymorphism was determined by allelic discrimination TaqMan assay. Male carriers of the AA genotype had significantly lower plasma leptin levels than GA (p < 0.008) and GG (p < 0.001) carriers and significantly lower mean hip circumference (HC) values than GG carriers (p = 0.04). In girls, leptin levels were also lower in A-allele carriers than in GG carriers, and BMI and HC were significantly lower in AA carriers as compared with GG carriers. In addition, the frequency of the A allele was significantly lower (chi(2): 4.58, p = 0.032) in the OW-obese than in the NW group. In conclusion, the LEP G-2548A polymorphism is associated with variations in leptin levels, BMI and HC in Spanish pubertal children, and evidence suggests a link between the G allele and presence of overweight in girls.

Leptin and adiponectin levels in pubertal children: relationship with anthropometric variables and body composition.

BACKGROUND: Adipocytokines play an important role in controlling energy homeostasis, and in various metabolic processes related to obesity. The aim of this study was to describe serum leptin and adiponectin concentrations in a sample of pubertal Spanish children and to evaluate their association with anthropometric parameters and body composition. METHODS: The study included 833 pubertal boys and girls. Serum leptin and adiponectin concentrations were determined by ELISA. RESULTS: Leptin concentrations were significantly higher (p<0.0001) in obese or overweight (OW) children compared with children with normal weight (NW). Adiponectin was significantly lower (p<0.01) in obese or OW girls compared with girls of NW, although these findings were not the same for boys. Weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist to hip ratio were significantly correlated (p<0.01) with leptin concentrations in both genders. Correlation of leptin with fat mass and % fat mass was strong, particularly in boys. The association of adiponectin concentrations with anthropometric variables was weaker in both genders. No significant correlations were found between adiponectin concentrations and fat mass or % fat mass. CONCLUSIONS: In summary, our study showed that, in pubertal children, leptin is related to weight, BMI, WC and HC and correlates even more strongly with % fat mass. However, adiponectin was weakly related to anthropometric variables and was not correlated with body fat.

Sex hormone-binding globulin levels and metabolic syndrome and its features in adolescents.

BACKGROUND: Low levels of sex hormone-binding globulin (SHBG) are associated with obesity, insulin resistance, and metabolic syndrome (MS) in men and women, and it has been suggested that SHBG could be a useful marker for MS risk. OBJECTIVE: The aim of this study was to analyze the relationship of SHBG levels with MS and its components in Spanish adolescents. METHODS: The sample population of this cross-sectional study was comprised of 386 male and 429 female adolescents, aged 12-16 yr. Anthropometric parameters and blood pressure (BP) were measured. Total cholesterol, high-density lipoprotein (HDL)-cholesterol, insulin, glucose, and SHBG levels were determined. The pediatric International Diabetes Federation (IDF) definition was used to classify adolescents for MS. RESULTS: SHBG levels were lower in adolescents with MS or with some MS features. More than 90% of the abdominally obese adolescents were in the lowest and medium SHBG tertiles. In girls, BP was significantly higher in the lowest SHBG tertile than in the two others, whereas in boys BP levels were significantly higher in the lowest and medium tertiles than in the highest one. Insulin levels and homeostasis model assessment (HOMA) index were also significantly higher in the lowest SHBG tertile than in the two others. CONCLUSIONS: The associations of SHBG with MS and its components, such as abdominal obesity, high BP or insulin levels, are already present in normal adolescents. This may suggest the possibility of using SHBG levels as a biomarker for MS risk in adolescents as well as adults.

Sex hormone-binding globulin and lipid profile in pubertal children.

Men and women have different lipid profiles throughout life, related to changes in sex hormones; and this has been associated with sex-related differences in the prevalence of coronary heart disease. The influence of sex hormone changes during puberty on the lipid profile has been reported, but levels of sex hormone-binding globulin (SHBG) (the specific plasma binding protein of sex hormones) have not been evaluated even though its regulatory role might be crucial. The aim of this study was to analyze the relationship between sex hormones and SHBG and changes in plasma lipid levels during puberty. Our population-based sample included 370 healthy schoolchildren (175 male and 195 female), ranging from 12 to 15 years old. High-density lipoprotein cholesterol (HDL-C) levels were significantly lower in 15-year-olds than in younger boys, and apolipoprotein (apo) A-I levels steeply decreased across the studied age groups. Parallel to these changes, testosterone levels increased whereas SHBG decreased as age increases in boys. In girls, no significant differences were observed in these variables among the age groups. Testosterone and SHBG were highly correlated with anthropometric variables. Sex hormone-binding globulin was negatively associated with triglycerides (TG) in both sexes, remaining statistically significant after further adjustment for age and body mass index (BMI) in girls. Sex hormone-binding globulin was the only predictive variable for HDL-C and TG in multiple linear regression analysis, after adjustment by BMI, in both sexes, accounting for 10% of the variance of HDL-C in boys and for around 5% of the variance of TG in both sexes. In boys, testosterone and SHBG remained significantly correlated to apo A-I levels, even after adjusting for age and BMI, and were the most important predictive variables for apo A-I in multiple linear regression analysis. In conclusion, SHBG levels are related to a decrease in HDL-C and apo A-I levels during puberty in boys and to a decrease in TG levels during puberty in both sexes.

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.

Genetic determinants of plasma HDL-cholesterol levels in prepubertal children.

INTRODUCTION: Genetic determinants have been related to variation of high-density lipoprotein cholesterol (HDL-C) levels, but the extension of this association remains controversial. In our study, we analyzed the contribution of several polymorphisms on HDL-C-related genes to variation of plasma HDL-C in prepubertal children. METHODS: We studied 1269 (641 males and 628 females) 6-8 years old healthy children, who participated in a cross-sectional study examining cardiovascular risk factors in Spain. Common genetic variants in the apolipoprotein AI, apolipoprotein AII, cholesteryl ester transfer protein (CETP), hepatic lipase, ATP-binding cassette transporter A1, and paraoxonase genes were determined by PCR. RESULTS: CETP TaqI B2 carrier girls had significantly higher HDL-C levels than B1B1 girls. B2B2 boys had significantly higher (p<0.001) HDL-C than B1B1and B1B2 boys. In linear regression analysis, CETP TaqIB appears as the main predictor of HDL-C plasma levels, accounting for 4.5% and 1.8% of HDL-C variation in girls and boys respectively. CONCLUSIONS: Our data showed that among the studied polymorphisms only the CETP TaqIB polymorphism contributes to the variation in HDL-C levels in prepubertal children, particularly in girls, but overall these polymorphisms explain a small part of the variation of HDL-C plasma levels at this age.

[Serum folate levels in adolescent population in Madrid, Spain]. / Folato sérico en población adolescente de la Comunidad de Madrid.

BACKGROUND AND OBJECTIVE: Serum folate concentrations in children are essential to establish values which allow to compare different regions or countries, and raise the possibility of fortifying diet with group B vitamins and folic acid as a secondary prevention against cardiovascular diseases. SUBJECTS AND METHOD: A cross-sectional epidemiological study was performed to assess serum folate levels in school children, aged 13-15 years, in Madrid. Folate and vitamin B12 determinations were determined in blood samples of fasting children. Genotype C677T of methylentetrahydrofolate reductase (MTHFR) enzyme was determined by polymerase chain reaction. RESULTS: Average folate levels obtained in our study were 7.83 nmol/l (95% confidence interval, 7.42 to 8.23 nmol/l). Median was 6.89 nmol/l (interquartilic range: 5.30 to -9.30 nmol/l). No statistically significant differences were found by gender, age or presence of menstruation. Serum folate concentration decreased significantly with the mutation of the C677T genotype for MTHFR. Prevalence of deficits of folate (< 5.3 nmol/l) was 23.8% and raised significantly with the mutation of the C677T genotype for MTHFR: 18.8% for CC, 20.4% for CT, and 46.7% for TT. This effect was mainly observed in girls after menstruation. CONCLUSIONS: Homozygosis mutation in C677T genotype of the enzyme MTHFR induces lower folate levels, mainly in girls after menstruation. 5.3 nmol/l is proposed as a threshold to define deficient serum folate levels in the Spanish adolescent population.

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.

The serum levels of the EGF-like homeotic protein dlk1 correlate with different metabolic parameters in two hormonally different children populations in Spain.

BACKGROUND: The Dlk1 gene encodes for dlk1, a transmembrane protein belonging to the EGF-like repeat-containing family. Dlk1 has been shown to act as a regulator of adipogenesis. Fc-dlk1 transgenic mice show a decrease in adipose tissue and glucose tolerance, hypertriglyceridaemia and lower insulin sensitivity. Dlk1-deficient mice show growth retardation, increased serum lipid metabolites and develop obesity. These data advocate for a role of dlk1 in the maintenance of lipid homeostasis, and suggest that dlk1 levels may influence the development of cardiovascular disease. AIM AND METHODS: In this study, we analysed whether dlk1 serum levels could be indicative of the different hormonal or metabolic status shown by two Spanish children populations (6-8 years-old), Orense and Murcia. We determined dlk1 serum levels by ELISA assay, using an antibody raised against the recombinant protein, and performed a correlation analysis against measurements of several hormonal and biochemical parameters in samples from 494 subjects. RESULTS: We found a statistically significant positive correlation between serum levels of dlk1 and those of glucose (P < 0.05), total cholesterol (P < 0.01) and high-density lipoprotein-cholesterol (HDL-C) (P < 0.01) in children from Murcia, but not from Orense's population, where dehydroepiandrosterone-sulphate (DHEA-S) levels were significantly higher (P < 0.01) and dlk1 correlated positively with insulin (P < 0.01), homeostasis model assessment (HOMA) (P < 0.01) and free fatty acids (FFA) (P < 0.05). CONCLUSIONS: dlk1 serum levels appear related to the anabolic status of the children in association with changes in the levels of DHEA-S, which have been associated with hyperinsulinaemia and diabetes. Monitoring dlk1 levels may be important to evaluate the metabolic and hormonal stage of child development.

Hormone levels in 12- to 15-year-old boys and girls in Spain and their relationship with anthropometric variables.

OBJECTIVE: To determine hormone levels in a population-based sample of pubertal children and evaluate their association with anthropometric parameters. METHODS: Sex steroid levels were assessed using RIA and IRMA. RESULTS: In boys, changes in weight and height across the period were accompanied by changes in testosterone and SHBG. In girls, anthropometric variables did not change and were not correlated with estradiol. CONCLUSIONS: We observed an association between hormone levels and anthropometric changes when active growth associated with puberty was taking place.

[Cardiovascular risk factors in children. Main findings of the Four Provinces study]. / Factores de riesgo cardiovascular en la edad infantil. Resultados globales del estudio Cuatro Provincias.

Atherosclerosis is a process that begins during the first few decades of life, progresses asymptomatically, and generally shows no clinical manifestations until adulthood. The Spanish Four Provinces study, which involved 1275 prepubertal children, was an investigation into childhood risk factors for atherosclerosis (e.g., diet, anthropometric variables, lipid levels, and some genetic factors) that may be related to the occurrence of coronary artery disease in adults. In this review, we summarize the study's most important findings. The Four Provinces study showed that several factors associated with the metabolic syndrome (i.e., obesity, and raised glucose and triglyceride levels), which can lead to coronary disease in adults, are already present in schoolchildren. What is more, children from provinces with high coronary disease mortality weighed more and had higher plasma triglyceride and glucose levels. A high percentage of children in all provinces studied had total cholesterol and low-density lipoprotein cholesterol plasma levels above the recommended values. Despite the presence of some positive features in the population as a whole, such as a raised high-density lipoprotein cholesterol level and low prevalence of the apolipoprotein-E epsilon4 allele, which is known to be related to cardiovascular risk, if the metabolic changes described above persist, the risk of cardiovascular disease in Spain can only increase in the future. These metabolic characteristics are associated with a high-fat, low-carbohydrate diet which is far from that currently recommended for children. Correction of this poor diet at an early age would have significant benefits for the prevention of cardiovascular disease.

Dehydroepiandrosterone sulfate and high-density lipoprotein-cholesterol levels in overweight children.

OBJECTIVE: The association of childhood overweight with cardiovascular risk factors seems to change by sex and age, which may indicate that hormonal status could be the cause of this different association. In this study, we analyzed the relationship of dehydroepiandrosterone sulfate (DHEA-S) with the alterations associated with overweight by analyzing the influence of this hormone in the differences found in biochemical variables between normal-weight and overweight prepubertal children. RESEARCH METHODS AND DESIGN: The study included 684 6- to 8-year-old children (350 boys and 334 girls) categorized by the presence or absence of overweight, according to the age- and sex-specific cut-off points proposed for children. Lipid levels were determined by standard methods. DHEA-S and insulin levels were measured by radioimmunoassay. Biochemical variables were compared between normal-weight and overweight children by tertiles of DHEA-S. RESULTS: We observed that plasma high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein (apo)-AI levels were significantly lower in overweight than in normal-weight boys only in the highest tertile of DHEA-S. No significant differences in plasma glucose levels, total cholesterol, low-density lipoprotein-cholesterol, or apo B were found between overweight and normal-weight children in any DHEA-S tertile. In a Spearman correlation analysis, we observed a significant and negative correlation for weight and BMI with HDL-C and for weight and apo-AI levels only in the highest tertile of DHEA-S. DISCUSSION: Our study showed that, in our prepubertal population, the association of overweight with decreased HDL-C and apo-AI levels was present only in boys within the highest levels of DHEA-S, supporting the importance of hormonal influences on the association of metabolic alterations with overweight.

Metabolic adaptation in the crew of the Hesperides on their Antarctic journey.

AIMS: We studied the metabolic changes that took place in the crew of the Hesperides vessel in their 2001-2002 Antarctic journey, comparing two periods differing in diet and physical activity. METHODS AND RESULTS: Lipid profile, vitamin and hormone levels were analyzed in 17 subjects who completed the study in its two phases. In phase I the participants spent 47 days sailing with hard work and rough seas, and the diet was rich in fat and poor in fresh foods. In this phase, glucose decreased and HDL-cholesterol, apo-AI, and TSH increased. Plasma retinol and alpha-tocopherol levels remained stable, gamma-tocopherol, alpha-carotene and beta-carotene significantly decreased, and lycopene significantly increased. Phase II lasted 49 days including a 7-day long stop in port. This meant that a more varied diet was available and fresh foods were present in the hold. There was also less extreme physical activity. The metabolic pattern changed direction, glucose rose, HDL-cholesterol and apo-AI decreased and the levels of the vitamins that dropped in phase I started to increase. Lycopene significantly decreased. CONCLUSION: Contrary to popular beliefs about navigation at extreme latitudes, the metabolic changes described may be explained by the intense physical activity in a cold environment and a high-fat diet poor in fresh products.

Cholesterol and saturated fat intake determine the effect of polymorphisms at ABCG5/ABCG8 genes on lipid levels in children.

PURPOSE: Analysis of mutations in genes of the cholesterol metabolic pathway has not completely explained the interindividual variability of blood cholesterol concentrations attributed to gene-nutrient interactions. Thus, we analyzed polymorphisms in the ABCG5 and ABCG8 genes, involved in the regulation of intestinal cholesterol absorption, with special interest in a potential interaction with diet to determine lipid levels. METHODS: The polymorphisms ABCG5 C1950G (Gln604Glu) and ABCG8 C1895T (Ala640Val) were determined by polymerase chain reaction and restriction analysis in 1227 healthy school children, aged 6 to 8 years. RESULTS: No significant differences were found in blood lipid levels between subjects with different genotypes of the two analyzed polymorphisms. However, important differences appeared when separating subjects by their different lipid intake. The presence of the ABCG8 C1895T and ABCG5 C1950G polymorphisms was associated with different plasma total cholesterol, low-density lipoprotein cholesterol complex, and apolipoprotein B levels only in low-cholesterol consumers (significantly for the C1895T polymorphism), and among children within the lower tertile of saturated fat intake (significantly for the C1950G polymorphism). CONCLUSION: Polymorphisms at the half-transporter ABCG5 and ABCG8 genes affect blood cholesterol concentrations in prepubertal children by influencing dietary responsiveness. This highly significant gene-nutrient interaction could explain the great individual differences in the plasma lipid response to cholesterol and fat intake.

Dehydroepiandrosterone sulfate (DHEA-S) distribution in Spanish prepuberal children: relationship with fasting plasma insulin concentrations and insulin resistance.

BACKGROUND: The aim of this study was to analyze dehydroepiandrosterone sulfate (DHEA-S) levels in a population-based sample of Spanish prepuberal children and to investigate the relationship between DHEA-S and insulin. METHODS: 854 (440 boys and 414 girls) randomly selected prepuberal children were included in our study after a sampling. Children were 6 to 8 years old and were classified for the analysis in half-year intervals. DHEA-S and insulin levels were measured. RESULTS: DHEA-S levels increase significantly with age during prepuberty reaching the maximum level of DHEA-S for this period at 7.5 years old in girls and 8 years old in boys. Girls have significantly higher log DHEA-S levels than boys, except at the age of 8, where the levels are similar (median: 41.7 nmol/l girls and 41.1 nmol/l boys). DHEA-S correlates positively and significantly with weight, height, and BMI in all age intervals but the correlation between DHEA-S and insulin and HOMA is present only at the age of 6.5 in boys and 8 in girls. CONCLUSIONS: We report data about the distribution of DHEA-S in the Spanish prepuberal population. The maximum level of DHEA-S in this prepuberal period was reached before in girls than in boys, with girls having higher DHEA-S levels than boys until the end of this period. We found an important association between DHEA-S levels and weight, height and BMI but an inconsistent association of DHEA-S with insulin and HOMA.