Elevated circulating levels of lipoprotein-associated phospholipase A2 in obese children.

BACKGROUND: Obesity and cardiovascular disease (CVD) often co-exist, but the pathophysiologic mechanisms that link the two are not fully understood. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the modification of lipids within atheromatous plaques. Recently, circulating Lp-PLA2 was found to be predictive of thromboembolic episodes in adults, independently of a variety of other potential risk factors, including markers of inflammation, renal function, and hemodynamic stress. However, the function of this lipase and its importance as a biomarker in childhood obesity is much less studied. The aim of the study was to study Lp-PLA2, a non-traditional risk factor of CVD, in obese children. METHODS: Sixty-seven lean [39 boys and 28 girls, mean body mass index (BMI) z-score -0.2±0.8] and 66 obese (32 boys and 34 girls, mean BMI z-score 4.4±1.2) age-matched (p=0.251) children, aged 6-12 years, were studied. BMI z-score was calculated based on the Greek BMI growth curves, and children were categorized as obese according to the Cole criteria. All children underwent physical examination and a fasting morning blood sample was obtained for glucose, insulin, lipid profile, and Lp-PLA2 assessment. Plasma concentrations of Lp-PLA2 were determined by a commercially available Lp-PLA2 enzyme-linked immunosorbent assay kit (PLAC Test), while other measurements were performed using standard methods. RESULTS: Plasma Lp-PLA2 levels were significantly higher in obese children (322.5±77.8 ng/mL) compared with normal-weight ones (278.0±64.4 ng/mL, p<0.001). Lp-PLA2 concentrations were significantly correlated with the BMI z-score (p=0.004). Receiver operating characteristic analysis on Lp-PLA2 values resulted in significant areas under the curve (AUC) for distinguishing between obese and normal-weight groups of children (AUC, 0.726; p<0.001). CONCLUSIONS: We found significantly higher Lp-PLA2 levels in obese children than lean controls. Interestingly, they all had levels >200 ng/mL, which are considered to correlate with atherosclerosis and a high thromboembolic risk in adults. The positive correlation of Lp-PLA2 with BMI suggests that Lp-PLA2 might be the link between obesity and increased cardiovascular risk, which can be elevated even at a very young age. Measurement of Lp-PLA2 in plasma could therefore represent a further biomarker for assessing increased CVD risk in obese children and adolescents.

The Impact of Adiposity and Puberty on Thyroid Function in Children and Adolescents.

Background: In the context of a worldwide increase in childhood obesity, euthyroid hyperthyrotropinemia has been consistently reported and raises questions about its etiology, its potential metabolic complications, and its management. In this study we analyze the thyroid function with respect to BMI, pubertal status, and sex in children with obesity and discuss our results on an integrative context with the existent data from the literature. Methods: In this case-control study, we compared 389 children and adolescents with obesity to 158 controls. Age, sex, thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), BMI standard deviation score, and pubertal status were recorded. One factor-analysis of variance (ANOVA) was used with p < 0.05. Results: Mean serum TSH of children with obesity was higher (2.95 ± 1.2 mU/L) compared to normal weight group (2.42 ± 1.43 mU/L) (p < 0.0001). Only in females of both groups, serum TSH, T4, and T3 concentrations were all lower during puberty compared to prepuberty. In prepubertal girls and boys with obesity, a statistically significant correlation between TSH and BMI was found (r = 0.32, p = 0.012 and r = 0.47, p < 0.001, respectively), which is not sustained during puberty. Conclusions: Our results confirm the TSH elevation in children with obesity and indicates that puberty and adiposity have a differential sex-dependent impact on thyroid axis function.

The combined effect of MC4R and FTO risk alleles on childhood obesity in Greece.

OBJECTIVE: Single nucleotide polymorphism (SNP) risk alleles of obesogenic genes, such as the fat mass and obesity-associated protein (FTO) and the melanocortin-4 receptor (MC4R) gene, have been described in both paediatrics and adult populations. The aim of this study was to investigate the combined effect of FTO and MC4R risk alleles on the obese phenotype and metabolic profile of young children and adolescents of Greek origin. DESIGN: One hundred and fifty-three overweight and obese Greek children (mean age 11.08±2.23 years) and 151 age-matched normal-weight controls were enrolled. Along with anthropometric and standard biochemical profile genetic analysis for the high-risk rs9939609 A allele of the FTO gene and the high-risk C allele of the rs17782313 polymorphism downstream of the MC4R gene were investigated in all participants. RESULTS: The combined presence of three or more high-risk alleles of both the FTO and MC4R genes confers a 4-fold higher risk for obesity in children and adolescents of Greek origin, although these risk alleles have no impact on the metabolic alterations observed in these obese children and adolescents. CONCLUSIONS: There is a synergistic effect of the high-risk alleles of the FTO and MC4R genes on the obese phenotype, while no impact on the metabolic abnormalities was observed in Greek obese children and adolescents.

Association between polymorphisms in MTHFR and APOA5 and metabolic syndrome in the Greek population.

Impaired energy homeostasis and low-grade inflammation have been related to components of the metabolic syndrome (MetS) such as dyslipidemia, obesity, and insulin resistance. Single-nucleotide polymorphisms in the genes encoding for IL-6 (g.-634G>C; c.174G>C), TNFα (g.-308G>A), methylenetetrahydrofolate reductase (MTHFR) (c.677C>T), APOC3 (c.3175C>G), and APOA5 (g.-1131T>C) have been implicated in the processes of inflammation and energy intake that take place in the development of MetS manifestations. The aim of this study was to investigate the association between these polymorphisms and MetS, as defined by the National Cholesterol Education Program-Adult treatment Panel III criteria, in the Greek population. Overall, 30 unrelated subjects who met the criteria of MetS and 60 matched control subjects from central Greece were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. There was a significant association between both MTHFR c.677C>T (odds ratio: 4.02; confidence interval: 1.496-10.777; p=0.003) and APOA5 g.-1131T>C (odds ratio: 3.514; confidence interval: 1.065-11.585; p=0.035) and MetS. Analysis of constructed haplotypes showed a highly significant association between 677C-1131T-3175C haplotype and MetS (p<0.0001). Carriers of both MTHFR c.677T and APOA5 g.-1131C were associated with increased triglyceride levels (p=0.001 and p=0.003, respectively), compared with noncarriers. These results support a role for MTHFR and APOA5 as risk factors for MetS and suggest their further validation in larger independent populations.