Interplay of the Mediterranean diet and genetic hypertension risk on blood pressure in European adolescents: Findings from the HELENA study.

Early-life onset of high blood pressure is associated with the development of cardiovascular diseases in adulthood. In adolescents, limited evidence exists regarding the association between adherence to the Mediterranean Diet (MedDiet) and normal blood pressure (BP) levels, as well as its potential to modulate genetic predisposition to HTN. This study investigated the interaction between a MedDiet score and a recently developed HTN-genetic risk score (HTN-GRS) on blood pressure levels in a European adolescent cohort. The MedDiet score was derived from two non-consecutive 24-h dietary recalls and ranged from 0 (indicating low adherence) to 9 (indicating high adherence). Multiple linear regression models, adjusted for covariates, were employed to examine the relationship between the MedDiet score and BP z-scores and to assess the interaction effects between the MedDiet score and HTN-GRS on BP z-scores. MedDiet score showed a negative association with z-systolic BP (SBP) (ß = -0.40, p < 0.001) and z-diastolic BP (DBP) (ß = -0.29, p = 0.001). Additionally, a significant interaction effect was identified between the MedDiet score and HTN-GRS on z-SBP (ß = 0.02, p < 0.001) and z-DBP (ß = 0.02, p < 0.001). The modulatory effect of the MedDiet was more pronounced in females than in males, and HTN-GRS exhibited a stronger influence on DBP than on SBP.   Conclusion: The study suggests that higher adherence to the MedDiet is associated with reduced BP levels in adolescents and provides evidence of a genetic-diet interaction influencing BP in adolescents. What is Known: • Adherence to the Mediterranean diet may reduce BP levels. What is New: • It is the first study to assess the connection between adherence to a Mediterranean diet, a hypertension genetic risk score, and how they interact in influencing blood pressure. • It is conducted within a multicenter cohort of European adolescents.

Longitudinal associations between cardiovascular biomarkers and metabolic syndrome during puberty: the PUBMEP study.

Puberty has been described as a life stage of considerable metabolic risk specially for those with obesity. The low-grade systemic inflammatory status associated with obesity could be one of the connections with metabolic syndrome (MetS). Thus, we aimed to assess the relationship between inflammatory and cardiovascular biomarkers and the development of MetS during puberty. Seventy-five children from the PUBMEP study (33 females), aged 4-18 years, were included. Cardiovascular and inflammatory biomarkers were measured in the prepubertal and pubertal stage, including high-sensitivity C-reactive protein (CRP), leptin, tumor necrosis factor-alpha (TNFα), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP-1), total plasminogen activator inhibitor-1 (tPAI), resistin, adiponectin, myeloperoxidase (MPO), and soluble intercellular adhesion molecule-1 (sICAM-1). MetS was diagnosed at each measurement point. Mixed-effects and logistic regressions were performed. Those children with MetS in puberty presented higher prepubertal values of several cardiometabolic biomarkers in comparison to those without MetS (z-score body mass index (zBMI), waist circumference, insulin, HOMA-IR, leptin, and tPAI (p < 0.05)). For prepubertal children with obesity, the odds of developing MetS in puberty were significantly higher in those having high zBMI (OR = 4.27; CI: 1.39-22.59) or high concentrations of tPAI (OR = 1.19; CI: 1.06-1.43). CONCLUSION: Those with obesity with higher prepubertal tPAI plasma levels had 19% higher odds of having MetS at puberty highlighting the existence of association between MetS, obesity, and inflammation already in puberty. Thus, assessing cardiometabolic and inflammatory status in children with obesity already at prepuberty is key to avoiding future comorbidities. WHAT IS KNOWN: • Inflammation, metabolic syndrome, and obesity may have their onset in childhood. • Puberty is a life stage characterized for an increased cardiovascular risk. WHAT IS NEW: • Prepuberty state could be an early indicator of future cardiometabolic risk. • Children with obesity and high total plasminogen have higher odds of future metabolic syndrome.

Interplay of physical activity and genetic variants of the endothelial lipase on cardiovascular disease risk factors.

BACKGROUND: The aim of this study was to investigate the association of endothelial lipase gene (LIPG) polymorphisms with cardiovascular disease (CVD) risk factors in adolescents and their interaction with physical activity. METHODS: Six polymorphisms of LIPG were genotyped in 1057 European adolescents (12-18 years old) enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study. CVD risk factors related to lipid profile, blood pressure, adiposity and glucose regulation were recorded. Physical activity was objectively measured by accelerometry. RESULTS: The major C allele of rs2000813, the minor T allele of rs2276269 and the minor G allele of rs9951026 were associated with lower levels of several CVD risk factors related to lipid profile. We also found a significant association of the TTACA LIPG haplotype (rs2000812, rs2000813, rs8093249, rs2276269 and rs9951026) with higher concentrations of low-density cholesterol and apolipoprotein B. Finally, the interaction between physical activity and the polymorphisms rs2000813, rs2276269 and rs9951026 had a significant influence on several CVD risk factors. CONCLUSIONS: LIPG polymorphisms were significantly associated with CVD risk factors in European adolescents. Interestingly, alleles of these polymorphisms were associated with a better cardiovascular profile in physically active adolescents only. High physical activity may reduce the development of CVD, modulating its genetic risk. IMPACT: Using gene-phenotype and gene × environment analyses, we detected associations between the endothelial lipase gene and cardiovascular risk factors, along with interactions with physical activity. This study shows that physical activity may modulate the influence of LIPG gene on cardiovascular risk in adolescents. These results bring insights into the mechanisms by which physical activity positively influences CVD in adolescents.

Impact of Physical Activity Intensity Levels on the Cardiometabolic Risk Status of Children: The Genobox Study.

Childhood obesity has been related to metabolic syndrome and low-grade chronic inflammation. This study aimed to evaluate the impact of physical activity intensities and practice on inflammation, endothelial damage, and cardiometabolic risk factors in children. There were 513 participants, aged 6-14 years, recruited for the study. Physical activity was measured by accelerometry, and the children were classified into four groups according to quartiles of moderate to vigorous physical activity (MVPA) practice as very low active, low active, moderate active, and high active. Anthropometric measures, blood pressure, and plasma metabolic and proinflammatory parameters were analyzed. Very low active group presented a worse lipid profile and higher insulin, leptin, adiponectin, resistin, matrix metallopeptidase-9, and tissue plasminogen activator inhibitor-1, while lower levels of tumor necrosis factor-alpha, Type 1 macrophages, and interleukin 8 than high-active children. Regression analyses showed that a higher MVPA practice was associated with lower levels of triacylglycerols (ß: -0.118; p = .008), resistin (ß: -0.151; p = .005), tPAI (ß: -0.105; p = .046), and P-selectin (ß: -0.160; p = .006), independently of sex, age, and body mass index (BMI). In contrast, a higher BMI was associated with higher levels of insulin (ß: 0.370; p < .001), Homeostasis Model Assessment (ß: 0.352; p < .001), triacylglycerols (ß: 0.209; p < .001), leptin (ß: 0.654; p < .001), tumor necrosis factor-alpha (ß: 0.182; p < .001), Type 1macrophages (ß: 0.181; p < .001), and tissue plasminogen activator inhibitor (ß: 0.240; p < .001), independently of sex, age, and MVPA. A better anthropometric, metabolic, and inflammatory profile was detected in the most active children; however, these differences were partly due to BMI. These results suggest that a higher MVPA practice and a lower BMI in children may lead to a better cardiometabolic status.

Association between CNTF Polymorphisms and Adiposity Markers in European Adolescents.

OBJECTIVE: To examine the association between polymorphisms of the ciliary neurotrophic factor gene (CNTF) and total and central adiposity markers in adolescents. STUDY DESIGN: This cross-sectional study involved 1057 European adolescents aged 12-18 years enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. Five polymorphisms of CNTF were genotyped, and the weight, height, waist and hip circumference, and triceps and subscapular skinfold thickness of the subjects were measured and recorded. RESULTS: The T allele of rs2509914, the C allele of rs2515363, and the G allele of rs2515362 were significantly associated (after Bonferroni correction) with higher values for several adiposity markers under different inheritance models. The CNTF CCGGA haplotype (rs2509914, rs17489568, rs2515363 rs1800169, and rs2515362) was also significantly associated with lower body mass index, waist circumference, waist/height ratio, and waist/hip ratio values compared with the TCCGG haplotype under several inheritance models. CONCLUSIONS: Three polymorphisms-rs2509914, rs2515363, and rs2515362-and the CCGGA haplotype of CNTF were significantly associated with adiposity in European adolescents. These results suggest the potential role of CTNF in the development of obesity-related phenotypes.

Total Polyphenol Intake Is Inversely Associated with a Pro/Anti-Inflammatory Biomarker Ratio in European Adolescents of the HELENA Study.

BACKGROUND: Although high dietary polyphenol intake is negatively associated with risk of certain inflammation-associated chronic diseases, the underlying mechanisms are not fully understood and few studies have explored this in adolescents. OBJECTIVE: This study aimed to evaluate the association between intakes of total polyphenols, polyphenol classes, and the 10 most commonly consumed individual polyphenols with inflammatory biomarkers in the blood of European adolescents. METHODS: In the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study, 526 adolescents (54% girls; 12.5-17.5 y) had data on inflammatory biomarkers and polyphenol intake from 2 nonconsecutive 24-h recalls via matching with the Phenol-Explorer database. Inflammatory biomarkers in serum were IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, transforming growth factor ß1 (TGF-ß1), TNF-α, IFN-γ, soluble vascular adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin (sE-selectin), white blood cells, lymphocytes, T cells, and C-reactive protein. Multilevel linear models were used to test associations of polyphenol intake with a pro/anti-inflammatory biomarker ratio [(zTNF-α + zIL-6 + zIL-1)/3/zIL-10] as well as with separate inflammatory biomarkers, adjusted for sociodemographic variables, diet inflammation index, BMI z score, and serum triglycerides. RESULTS: The pro/anti-inflammatory biomarker ratio was linearly inversely associated with the intake of total polyphenols (ß = -0.11, P = 0.040). When other inflammation biomarkers were considered, the serum IL-10 concentration was inversely associated with total polyphenol (ß = -0.12, P = 0.017) and flavonoid (ß = -0.12, P = 0.013) intakes, findings that were inconsistent with the biomarker ratio results. However, the anti-inflammatory capacity of polyphenols was confirmed by positive associations of IL-4 with phenolic acid (ß = 0.09 P = 0.049) and stilbene (ß = 0.13, P = 0.019) intakes and the negative association of IL-1, IL-2, and IFN-γ with lignan intake (ß = -0.10, P = 0.034; ß = -0.09, P = 0.049; ß = -0.11, P = 0.023). CONCLUSIONS: The negative relation with the overall pro/anti-inflammatory biomarker ratio suggests a potential anti-inflammatory role of high polyphenol intakes among European adolescents. Nevertheless, associations are dependent on polyphenol type and the inflammatory biomarker measured.

Association of UCP1, UCP2 and UCP3 gene polymorphisms with cardiovascular disease risk factors in European adolescents: the HELENA study.

BACKGROUND: Cardiovascular diseases (CVDs) are responsible for 31% of all deaths worldwide. Genetic predisposition to CVDs in adolescents remains largely unknown. The aim of this study was to examine the association of UCP1, UCP2 and UCP3 gene polymorphisms with CVD risk factors in European adolescents. METHOD: A cross-sectional study that involves 1.057 European adolescents (12-18 years old) from the HELENA study. A total of 18 polymorphisms of UCP1, UCP2 and UCP3 genes were genotyped. We measured serum total cholesterol, high-density lipoprotein,low-density lipoprotein, ApoA1, ApoB, leptin, triglycerides, glucose, insulin and blood pressure, and calculated HOMA (homeostatic model assessment), Quantitative Insulin Sensitivity Check Index (QUICKI) and a CVD risk score. RESULTS: The G allele of UCP2 rs2735572 and T allele of UCP2 rs17132534 were associated with higher diastolic blood pressure (P = 0.001; false discovery rate [FDR] = 0.009 and P = 8e-04; FDR = 0.009, respectively). We observed that the AATAG haplotype of UCP1 was associated with higher serum ApoB/ApoA1 (P = 0.008; FDR = 0.031) and ApoB levels (P = 0.008; FDR = 0.031). Moreover, the ACC haplotype of UCP3 was associated with a higher CVD risk score (P = 0.0036; FDR = 0.01). CONCLUSIONS: Two UCP2 polymorphisms and haplotypes of UCP1 and UCP3 were associated with CVD risk factors. These findings suggest that UCPs may have a role in the development of CVD already in adolescents.

Association between lipoprotein lipase gene polymorphisms and cardiovascular disease risk factors in European adolescents: The Healthy Lifestyle in Europe by Nutrition in Adolescence study.

OBJECTIVES: To examine the association of lipoprotein lipase (LPL) polymorphisms with cardiovascular disease (CVD) risk factors in European adolescents, along with the influence of physical activity on these associations. METHODS: A total of 13 LPL polymorphisms were genotyped in 1.057 European adolescents (12-18 years old) from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. Serum lipids, glucose, insulin, and leptin (LEP) levels were measured and a CVD risk score was computed. We also measured body weight and height, waist and hip circumferences, and triceps and subscapular skinfold thickness. Physical activity was objectively measured by accelerometry for 7 days. RESULTS: The rs1534649, rs258, rs320, and rs328 polymorphisms were associated with several CVD risk factors (ie, body mass index, triglycerides [TG], LEP, and cholesterol/high-density lipoprotein [HDL], low-density lipoprotein [LDL]/HDL, TG/HDL ratios). TG and TG/HDL were associated with haplotype blocks 3 (rs282, rs285 polymorphisms) and 4 (rs3126, rs320, rs328, rs10099160 polymorphisms), being the latter also associated with the CVD risk score. Physical activity modulated the association of adiposity with rs1534649 and rs258 polymorphisms. CONCLUSIONS: Polymorphisms rs1534649, rs258, rs320 and rs328, and two haplotypes of LPL were significantly associated with CVD risk factors in European adolescents. Higher levels of moderate to vigorous physical activity may attenuate the effects of rs1534649 and rs258 polymorphisms on adiposity.

Dietary sugars, metabolic effects and child health.

PURPOSE OF REVIEW: To describe current findings on sugar intake in children worldwide, including sugar sources and their impact on child health focusing on cardiometabolic alterations usually associated to obesity. RECENT FINDINGS: In children less than 4 years, intakes of added sugars across countries ranged from 9.8 to 11.2% of total energy; in children 4-10 years, it ranged from less than 3-18%; and in adolescents, it ranged from 13.6 to 16.6%. For most countries, intakes of added sugars were greater than the recommended upper limit of 10% of total energy for children and adolescents and less or around 10% in infants. In most studies, soft drinks and fruit-based drinks accounted for the greatest proportion of the added sugars intake, followed by milk products and sweet bakery products. High added sugar intake has been associated with increased obesity risk and fat deposition in the liver, contributing to dyslipidemia, high blood pressure, insulin resistance and cardio-metabolic risk. SUMMARY: As a high added sugar intake is associated with cardio-metabolic conditions in children and adolescents, the current scenario supports the need for stronger targeted long-term policies that prevent the excessive sugar intake in young populations.

Lifestyle patterns and endocrine, metabolic, and immunological biomarkers in European adolescents: The HELENA study.

OBJECTIVE: To evaluate the association of lifestyle patterns related to physical activity (PA), sedentariness, and sleep with endocrine, metabolic, and immunological health biomarkers in European adolescents. METHODS: The present cross-sectional study comprised 3528 adolescents (1845 girls) (12.5-17.5 years) enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence Study. Cluster analysis was performed by including body composition, PA by accelerometry, self-reported sedentary behaviors, and sleep duration. We also measured endocrine, metabolic, and immunological biomarkers. RESULTS: Three-cluster solutions were identified: (a) light-PA time, moderate-vigorous-PA time and sedentary time, (b) light-PA time, moderate-vigorous-PA time, sedentary time and sleep time, (c) light-PA time, moderate-vigorous-PA time, sedentary time and body composition. In addition, each cluster solution was defined as: "healthy," "medium healthy," and "unhealthy" according to the presented rating. Analysis of variance showed that overall the healthiest groups from the three clusters analyzed presented a better metabolic profile. A decision tree analysis showed that leptin had a strong association with cluster 3 in both boys and girls, high-density lipoprotein cholesterol had the strongest association with clusters 1 and 3 in boys. Cortisol had the strongest association with cluster 1. HOMA index (homeostatic model assessment) and C3 showed a strong association with cluster 3 in girls. CONCLUSIONS: Our results support the existence of different interactions between metabolic health and lifestyle patterns related to PA, sedentariness, and sleep, with some gender-specific findings. These results highlight the importance to consider multiple lifestyle-related health factors in the assessment of adolescents' health to plan favorable strategies.

Leptin Receptor Gene Variant rs11804091 Is Associated with BMI and Insulin Resistance in Spanish Female Obese Children: A Case-Control Study.

Leptin is an endocrine hormone that has a critical role in body weight homoeostasis and mediates its effects via the leptin receptor (LEPR). Common polymorphisms in the genes coding leptin receptors have been associated with metabolic abnormalities. We assessed the association of 28 LEPR polymorphisms with body mass index (BMI) and their relationship with obesity-related phenotypes, inflammation and cardiovascular disease risk biomarkers. A multicentre case-control study was conducted in 522 children (286 with obesity and 236 with normal-BMI). All anthropometric, metabolic factors and biomarkers were higher in children with obesity except apolipoprotein (Apo)-AI, cholesterol, high-density lipoprotein cholesterol (HDL-c), and adiponectin, which were lower in the obesity group; and glucose, low-density lipoprotein cholesterol (LDL-c), and matrix metalloproteinase-9 that did not differ between groups. We identified the associations between rs11208659, rs11804091, rs10157275, rs9436303 and rs1627238, and BMI in the whole population, as well as the association of rs11804091, rs10157275, and rs1327118 with BMI in the female group, although only the rs11804091 remained associated after Bonferroni correction (p = 0.038). This single nucleotide polymorphisms (SNP) was also associated with insulin (p = 0.004), homeostasis model assessment for insulin resistance (HOMA-IR) (p = 0.006), quantitative insulin sensitivity check index (QUICKI) (p = 0.005) and adiponectin (p = 0.046) after adjusting for age, Tanner stage and BMI. Our results show a sex-specific association between the rs11804091 and obesity suggesting an influence of this SNP on insulin resistance.

Cell Models and Their Application for Studying Adipogenic Differentiation in Relation to Obesity: A Review.

Over the last several years, the increasing prevalence of obesity has favored an intense study of adipose tissue biology and the precise mechanisms involved in adipocyte differentiation and adipogenesis. Adipocyte commitment and differentiation are complex processes, which can be investigated thanks to the development of diverse in vitro cell models and molecular biology techniques that allow for a better understanding of adipogenesis and adipocyte dysfunction associated with obesity. The aim of the present work was to update the different animal and human cell culture models available for studying the in vitro adipogenic differentiation process related to obesity and its co-morbidities. The main characteristics, new protocols, and applications of the cell models used to study the adipogenesis in the last five years have been extensively revised. Moreover, we depict co-cultures and three-dimensional cultures, given their utility to understand the connections between adipocytes and their surrounding cells in adipose tissue.

Genetics of oxidative stress in obesity.

Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs) in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications.

Eating Behaviours and Dietary Intake in Children and Adolescents: A Systematic Review.

PURPOSE OF REVIEW: This systematic review aimed to examine existing evidence related to associations between eating behaviours and dietary intake in children and adolescents, with a focus on the Children Eating Behaviour Questionnaire (CEBQ) and the Dutch Eating Behaviour Questionnaire (DEBQ) as assessment tools. RECENT FINDING: We conducted a systematic review following PRISMA guidelines. We included observational and interventional studies published in English, Spanish, or Portuguese, that evaluated the association between eating behaviours and food and beverage intake. Thirteen studies from nine countries met the inclusion criteria, with sample sizes ranging from 62 to 4,914 individuals aged 2 to 16 years-old. Ten studies used the CEBQ, and three used the DEBQ. Our retrieved studies showed that children and adolescents engaging in food approach behaviours tend to consume foods rich in sugar and fats. However, we observed a higher consumption of fruits and vegetables. On the other hand, children and adolescents with lower engagement to food avoidant behaviours, generally exhibited a lower overall food consumption, except for snacks, which they consumed at a higher rate. This systematic review suggests that eating behaviours play an important role in shaping dietary intake. Nevertheless, due to the heterogeneity related to eating behaviours and diet intake, it highlights the need for further research to understand these complex relationships to develop effective interventions for promoting healthy eating habits in children and adolescents.

Influence of FTO variants on obesity, inflammation and cardiovascular disease risk biomarkers in Spanish children: a case-control multicentre study.

BACKGROUND: Variants in the FTO gene have been associated with obesity in children, but this association has not been shown with other biomarkers. We assessed the association of 52 FTO polymorphisms, spanning the whole gene, with obesity and estimated the influence of these polymorphisms on anthropometric, clinical and metabolic parameters as well as inflammation and cardiovascular disease (CVD) risk biomarkers among Spanish children. METHODS: A multicentre case-control study was conducted in 534 children (292 obese and 242 with normal-BMI). Anthropometric, clinical, metabolic, inflammation and CVD risk markers were compared using the Student's t-test for unpaired samples. The genotype relative risk was assessed by comparing the obese and normal-BMI group, calculating the odds ratio. The association of each SNP with phenotypic parameters was analysed using either logistic or linear regression analysis. RESULTS: All anthropometric, clinical and metabolic factors as well as inflammatory and CVD risk biomarkers were higher in the obese than in the normal-BMI group, except adiponectin and HDL-c that were lower, and glucose, LDL-c, and metalloproteinase-9 that did not show difference. Four polymorphisms (rs9935401, rs9939609, rs9928094 and rs9930333) were positively associated with obesity and in linkage disequilibrium between each other; the haplotype including the risk alleles of these polymorphisms showed a high risk for obesity. The rs8061518 was negatively associated with obesity and the haplotype including this SNP and rs3826169, rs17818902 and rs7190053 showed a decreased risk for obesity. Additionally, the rs8061518 was associated with weight, diastolic blood pressure, insulin, homeostatic model assessment of insulin resistance, leptin, and active plasminogen inhibitor activator-1 after sex and age adjustment; however, after an additional BMI adjustment, this polymorphism remained associated only with leptin. CONCLUSIONS: We validated the previous reported association of genetic variability in intron 1 of the FTO gene with the risk of obesity and found no association with other related traits in this region of the gene. We have observed strong statistical evidence for an association of rs8061518 in intron 3 of the gene with decreased risk of obesity and low concentration of leptin.

KLB and NOX4 expression levels as potential blood-based transcriptional biomarkers of physical activity in children.

Insufficient physical activity (PA) in children is considered one of the major contributors to obesity and cardiometabolic complications later in life. Although regular exercise may contribute to disease prevention and health promotion, reliable early biomarkers are required to objectively discern people performing low PA from those who exercise enough. Here, we aimed to identify potential transcript-based biomarkers through the analysis of a whole-genome microarray in peripheral blood cells (PBC) from physically less active (n = 10) comparing with more active (n = 10) children. A set of genes differentially expressed (p < 0.01, Limma test) in less physically active children were identified, including the down-regulation of genes related to cardiometabolic benefits and improved skeletal function (KLB, NOX4, and SYPL2), and the up-regulation of genes whose elevated expression levels are associated with metabolic complications (IRX5, UBD, and MGP). The analysis of the enriched pathways significantly affected by PA levels were those associated with protein catabolism, skeletal morphogenesis, and wound healing, among others, which may suggest a differential impact of low PA on these processes. Microarray analysis comparing children according to their usual PA has revealed potential PBC transcript-based biomarkers that may be useful in early discerning children expending high sedentary time and its associated negative consequences.

Development of a genetic risk score to predict the risk of hypertension in European adolescents from the HELENA study.

Introduction: From genome wide association study (GWAS) a large number of single nucleotide polymorphisms (SNPs) have previously been associated with blood pressure (BP) levels. A combination of SNPs, forming a genetic risk score (GRS) could be considered as a useful genetic tool to identify individuals at risk of developing hypertension from early stages in life. Therefore, the aim of our study was to build a GRS being able to predict the genetic predisposition to hypertension (HTN) in European adolescents. Methods: Data were extracted from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study. A total of 869 adolescents (53% female), aged 12.5-17.5, with complete genetic and BP information were included. The sample was divided into altered (≥130 mmHg for systolic and/or ≥80 mmHg for diastolic) or normal BP. Based on the literature, a total of 1.534 SNPs from 57 candidate genes related with BP were selected from the HELENA GWAS database. Results: From 1,534 SNPs available, An initial screening of SNPs univariately associated with HTN (p < 0.10) was established, to finally obtain a number of 16 SNPs significantly associated with HTN (p < 0.05) in the multivariate model. The unweighted GRS (uGRS) and weighted GRS (wGRS) were estimated. To validate the GRSs, the area under the curve (AUC) was explored using ten-fold internal cross-validation for uGRS (0.802) and wGRS (0.777). Further covariates of interest were added to the analyses, obtaining a higher predictive ability (AUC values of uGRS: 0.879; wGRS: 0.881 for BMI z-score). Furthermore, the differences between AUCs obtained with and without the addition of covariates were statistically significant (p < 0.05). Conclusions: Both GRSs, the uGRS and wGRS, could be useful to evaluate the predisposition to hypertension in European adolescents.

Prepubertal Children With Metabolically Healthy Obesity or Overweight Are More Active Than Their Metabolically Unhealthy Peers Irrespective of Weight Status: GENOBOX Study.

Background and Aim: The association of a metabolically healthy status with the practice of physical activity (PA) remains unclear. Sedentarism and low PA have been linked to increased cardiometabolic risk. The aim of this study was to evaluate the PA levels in metabolically healthy (MH) or unhealthy (MU) prepubertal children with or without overweight/obesity. Methods: A total 275 children (144 boys) with 9 ± 2 years old were selected for the GENOBOX study. PA times and intensities were evaluated by accelerometry, and anthropometry, blood pressure, and blood biochemical markers were analyzed. Children were considered to have normal weight or obesity, and further classified as MH or MU upon fulfillment of the considered metabolic criteria. Results: Classification resulted in 119 MH children (21% with overweight/obesity, referred to as MHO) and 156 MU children (47% with overweight/obesity, referred to as MUO). Regarding metabolic profile, MHO showed lower blood pressure levels, both systolic and diastolic and biochemical markers levels, such as glucose, Homeostatic Model Assessment of Insulin Resistance, triglycerides and higher HDL-c levels than MUO (P < 0.001). In addition, MHO children spent more time in PA of moderate intensity compared with MUO children. In relation to vigorous PA, MH normal weight (MHN) children showed higher levels than MUO children. Considering sex, boys spent more time engaged in moderate, vigorous, and moderate-vigorous (MV) PA than girls, and the number of boys in the MH group was also higher. Conclusion: Prepubertal MHO children are less sedentary, more active, and have better metabolic profiles than their MUO peers. However, all children, especially girls, should increase their PA engagement, both in terms of time and intensity because PA appears to be beneficial for metabolic health status itself.

Height-based equations as screening tools for high blood pressure in pediatric practice, the GENOBOX study.

Due to the absence of easily applicable cut-off points to determine high blood pressure or hypertension in children, as in the adult population, blood pressure is rarely measured in the pediatrician's clinical routine. This has led to an underdiagnosis of high blood pressure or hypertension in children. For this reason, the present study evaluate the utility of five equations for the screening of high blood pressure in children: blood pressure to height ratio, modified blood pressure to height ratio, new modified blood pressure to height ratio, new simple formula and height-based equations. The authors evaluated 1599 children between 5 and 18 years. The performance of the five equations was analyzed using the receiver-operating characteristics curves for identifying blood pressure above P90th according to the American Academy of Pediatrics Clinical Practice Guideline 2017. All equations showed an area under the curve above 0.882. The new modified blood pressure to height ratio revealed a high sensitivity whereas the height-based equations showed the best performance, with a positive predictive value above 88.2%. Finally, all equations showed higher positive predictive values in children with overweight or obesity. The height-based equation obtained the highest PPV values above 71.1% in children with normal weight and above 90.2% in children with overweight or obesity. In conclusions, the authors recommend the use of the height-based equations equation because it showed the best positive predictive values to identify children with elevated blood pressure, independently of their sex, pubertal and weight status.

Are Peripheral Biomarkers Determinants of Eating Styles in Childhood and Adolescence Obesity? A Cross-Sectional Study.

Disturbances in eating behaviors have been widely related to obesity. However, little is known about the role of obesity-related biomarkers in shaping habitual patterns of eating behaviors (i.e., eating styles) in childhood. The objective of the present study was to explore the relationships between several biomarkers crucially involved in obesity (ghrelin, insulin resistance, and leptin/adiponectin ratio) and eating styles in children and adolescents with obesity. Seventy participants aged between 8 and 16 (56.2% men) fulfilled the Spanish version of the Dutch Eating Behavior Questionnaire for Children to measure external, emotional, and restrained eating styles. In addition, concentrations of ghrelin, leptin, adiponectin, insulin, and glucose were obtained through a blood test. Hierarchical multiple regression analyses controlling for age and sex were computed for each eating style. Results indicated that individuals with higher ghrelin concentration levels showed lower scores in restrained eating (ß = -0.61, p < 0.001). The total model explained 32% of the variance of the restrained pattern. No other relationships between obesity-related biomarkers and eating behaviors were found. This study highlights that one of the obesity-risk factors, namely lower plasma ghrelin levels, is substantially involved in a well-known maladaptive eating style, restraint eating, in childhood obesity.