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Background and Aims: The early onset of cardio-metabolic abnormalities, known as metabolically unhealthy (MU) status, is highly associated with obesity and cardiovascular disease (CVD), as well as with increased morbidity and mortality later in life. Given the lack of a consensus MU classification for prepubertal children, we aimed to compare available MU definitions in terms of their association with CVD risk biomarkers.Methods and Results: A total of 930 prepubertal children (622 with overweight/obesity, 462 males) aged 5-10.9 years were recruited, anthropometric measures were taken and biomarkers were analyzed. Children were classified using eight MU definitions based on different cut-offs for blood pressure, triacylglycerides, high-density lipoprotein cholesterol, glucose and homeostasis model assessment for insulin resistance (HOMA-IR). MU prevalence in children with overweight/obesity ranged between 30% and 60% across definitions. Plasma concentrations of resistin, leptin, myeloperoxidase (MPO) and total plasminogen activator inhibitor 1 (tPAI-1) were higher, and those of adiponectin were lower, in MU compared to MH children with overweight/obesity. Linear regression analyses confirmed the contribution of MPO and tPAI-1 concentrations to MU status, with most significant results derived from definitions that use age and sex-specific criteria and that account for HOMA-IR.Conclusion: Plasma concentrations of MPO and tPAI-1 are increased in prepubertal MU children irrespective of having normal-weight or overweight/obesity. Inclusion of age and sex-specific cut-offs for cardio-metabolic components as well as insulin resistance criteria increases the quality of MU definitions as seen by their stronger association with CVD biomarkers concentrations. [ABSTRACT FROM AUTHOR]

Changes in paraoxonase 1 (PON1) activities have been observed in a variety of diseases involving oxidative stress, such as CVD. However, its role in obesity has not been fully established. In the present study, we aimed (1) to genotype sixteen PON1 SNP, (2) to measure serum PON1 activities and (3) to correlate these findings with the incidence of childhood obesity and related traits. We conducted a case–control study of 189 normal-weight and 179 obese prepubertal children, and we measured four different PON1 activities: lactonase; paraoxonase; arylesterase; diazoxonase. Although none of these activities was significantly different between the obese and normal-weight children, lactonase activity was found to be positively correlated with HDL-cholesterol and ApoA1 levels and negatively correlated with myeloperoxidase and fatty acid-binding protein 4 levels. Among the sixteen genotyped PON1 SNP, only the intronic SNP rs854566 exhibited a significant association with obesity (OR 0·61, 95% CI 0·41, 0·91; P=0·016). This genetic variant was also associated with increased diazoxonase, lactonase and arylesterase activities and decreased paraoxonase activity. Other genetic variants exhibited different association patterns with serum activities based on their location within the PON1 gene, and SNP that were located within the promoter were strongly associated with lactonase, arylesterase and diazoxonase activities. The functional variant Q192R exhibited the greatest effect on paraoxonase activity (P=5·88 × 10-42). In conclusion, SNP rs854566 was negatively associated with childhood obesity and with increased serum PON1 activities in prepubertal children. We determined that lactonase is a reliable indicator of PON1 activities and should be included in future studies of PON1 function. [ABSTRACT FROM AUTHOR]

Background:The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme catalyses the regeneration of active cortisol from inert cortisone and plays a critical role in tissue-specific corticosteroid reactions; therefore, 11β-HSD1 is a key molecule associated with the development of obesity. Despite evidence for its role in obesity, no genetic polymorphisms have been significantly associated with the disease per se.Objective:The aim of this study was to evaluate whether HSD11B1 gene variants, which have never been studied before, are associated with obesity and its related traits, as well as its relation to biomarkers of inflammation, liver damage and cardiovascular disease in a cohort of Spanish children.Design:We performed a prospective case-control study.Subjects:A total of 534 children were examined and classified as being obese (n=292) or normal weight (n=242). Anthropometric and biochemical measurements related to obesity, including inflammation, liver damage and cardiovascular disease, were determined. Genomic DNA was extracted and 10 HSD11B1 gene single-nucleotide polymorphisms (SNPs) were genotyped.Results:A novel SNP, rs3753519, was strongly associated with obesity and this SNP was the only statistically significant HSD11B1 gene SNP remaining after a Bonferroni correction (odds ratio=1.97 for allelic effect, 95% confidence interval 1.23-3.16; P=0.004 and Bonferroni corrected P=0.046). In addition, this SNP was significantly and positively associated with increased body mass index (BMI), BMI z-score, weight, waist circumference, plasma γ-glutamyl transpeptidase and plasma active plasminogen activator inhibitor 1. The SNP was negatively associated with plasma adiponectin and cortisol after adjusting for sex and age. None of the inflammation biomarkers tested were associated with the risk allele.Conclusion:These data, which link an HSD11B1 genotype with both disease prevalence and its related phenotypes, strongly support a role for the rs3753519 polymorphism in the pathogenesis of pediatric-onset obesity. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: It has been suggested that adipokine changes might precede changes in plasma non-esterified fatty acids and other obesity metabolic biomarkers. The aim of the present study was to evaluate changes in fasting and postprandial plasma levels of adiponectin, non-esterified fatty acids, and tumor necrosis factor-alpha in prepubertal obese children and age-matched normal-weight children. Methods and results: Fifty-four children of prepubertal age (34 obese, comprising 23 males and 11 females, and 20 normal-weight comprising 11 males and 9 females) were studied. A standard 438kcal breakfast was given to both groups. Baseline measurements included anthropometry and plasma lipids. The following parameters were determined in plasma before and after breakfast: glucose, insulin, and C-peptide at baseline and 2h and non-esterified fatty acids, adiponectin, and tumor necrosis factor-alpha at baseline and 1, 2, and 3h. Fasting plasma non-esterified fatty acid levels were lower in the obese versus normal-weight children (P =0.021). Both at baseline and postprandially, plasma adiponectin levels were lower in the obese versus normal-weight children (P <0.001). A trend was observed (P =0.06) that levels of tumor necrosis factor-alpha were lower in the obese versus normal-weight children. Adiponectin was inversely associated with insulin in the obese children after adjustment for BMI and sex (r =−0.401, P =0.025). Conclusion: At prepubertal age, obese children show lower fasting and postprandial plasma adiponectin levels in comparison to normal-weight children, whereas non-esterified fatty acids and tumor necrosis factor-alpha were not yet increased. Therefore, adiponectin appears to be a good marker of early metabolic alterations associated with childhood obesity. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the intake, plasma concentrations and postprandial response of trans fatty acids in obese and control children at prepubertal age in order to detect potential associations with childhood obesity.Design: Case-control study, clinical dietary intervention with a 428 kcal standardized breakfast and longitudinal 3 h postprandial follow-up for trans fatty acid plasma levels.Subjects: Fifty-four children aged 6-13 years of both sexes, 34 obese (body mass index >97th percentile for age and sex) and 20 non-obese (control group) at prepubertal period (Tanner I).Measurements: Various anthropometric parameters and sex hormones, fasting insulin and glucose, estimation of dietary trans fatty acid intake and their plasma quantitation in fasting conditions, and for 3 h following intake of a standardized breakfast.Results: Dietary trans fatty acid intake was less than 0.4% of total energy in both groups, with a trend towards higher intake in obese children. Fasting plasma trans fatty acid concentrations and percentages were similar in both groups. However, trans fatty acid levels at +3 h were significantly higher than at 0 h in obese children, but not in controls (obese, 0 h: 2.38+/-0.29; 3 h: 3.62+/-0.45; controls, 0 h: 2.29+/-0.24; 3.14+/-0.49 mg/dl); cis monounsaturated fatty acid concentrations were not significantly affected by the postprandial interval. Obese children exhibited hyperinsulinemia and insulin resistance; however, trans fatty acid intake or their plasma levels were not associated with them.Conclusion: There is a low intake of trans fatty acids in Southern Spanish children, which is supported by their low concentrations in plasma. No difference in trans fatty acid intake is observed between obese and control children, although plasma levels remain higher in obese than in control children after 3 h of a meal. A marked insulin resistance is seen in obese, but it is not correlated with either trans fatty acid intake or plasma concentration. [ABSTRACT FROM AUTHOR]