Dietary total antioxidant capacity is associated with leukocyte telomere length in a children and adolescent population.

BACKGROUND & AIMS: Oxidative stress and inflammation seem to be potential underlying mechanisms for telomere attrition. A lack of specific antioxidants is believed to increase free radical damage and a greater risk for telomere shortening. Our aim was to evaluate the relationship between diet and leukocyte telomere length in a cross-sectional study of children and adolescents. We hypothesized that dietary total antioxidant capacity would be positively associated with telomere length. METHODS: Telomere length was measured by quantitative real-time polymerase chain reaction in 287 participants (55% males, 6-18 years), who were randomly selected from the GENOI study. RESULTS: A positive correlation between dietary total antioxidant capacity and telomere length (r = 0.157, p = 0.007) was found after adjustment for age and energy intake. However, higher white bread consumption was associated with shorter telomeres (ß = -0.204, p = 0.002) in fully-adjusted models. Interestingly, those individuals who had simultaneously higher dietary total antioxidant capacity and lower white bread consumption significantly presented the longest telomeres. Moreover, the multivariable-adjusted odds ratio for very short telomeres was 0.30 for dietary total antioxidant capacity (p = 0.023) and 1.37 for white bread (p = 0.025). CONCLUSION: It was concluded that longer telomeres were associated with higher dietary total antioxidant capacity and lower white bread consumption in Spanish children and adolescents. These findings might open a new line of investigation about the potential role of an antioxidant diet in maintaining telomere length.

Common variants in genes related to lipid and energy metabolism are associated with weight loss after an intervention in overweight/obese adolescents.

BACKGROUND: Some SNPs related to lipid and energy metabolism may be implicated not only in the development of obesity and associated comorbidities, but also in the weight loss response after a nutritional intervention. OBJECTIVE: In this context, the present study analyzed four SNPs located within four genes known to be associated with obesity and other obesity-related complications, and their putative role in a weight-loss intervention in overweight/obese adolescents. METHODS: The study population consisted of 199 overweight/obese adolescents (13-16 yr old) undergoing 10 weeks of a weight loss multidisciplinary intervention: the EVASYON programme (www.estudioevasyon.org). Adolescents were genotyped for 4 SNPs, and anthropometric measurements and biochemical markers were analyzed at the beginning and after the intervention. RESULTS: Interestingly, APOA5(rs662799) was associated with the baseline anthropometric and biochemical outcomes, whereas FTO (rs9939609) seemed to be related with the change of these values after the 10-week intervention. The other two SNPs, located in the CETP (rs1800777) and the APOA1 (rs670) genes, showed important relationships with adiposity markers. Specifically, a combined model including both SNPs turned up to explain up to 24% of BMI-SDS change after 10 weeks of the multidisciplinary intervention, which may contribute to under - stand the weight loss response. CONCLUSION: Common variants in genes related to lipid and energy metabolism may influence not only biochemical outcomes but also weight loss response after a multidisciplinary intervention carried out in obese/overweight adolescents..

ANTECEDENTES: Algunas variantes genéticas relacionadas con el metabolismo lipídico y energético pueden estar implicadas en la respuesta a una intervención nutricional además de estar asociadas con el desarrollo de obesidad y comorbilidades asociadas. OBJETIVO: En este sentido, este artículo analiza cuatro polimorfismos situados en cuatro genes que han sido previamente asociados con la obesidad u otras complicaciones asociadas a la misma, así como su posible papel en la respuesta a una intervención para la pérdida de peso en adolescentes con sobrepeso u obesidad. MÉTODOS: La población en estudio está formada por 199 adolescentes con sobrepeso u obesidad (13-16 años) llevando a cabo una intervención multidisciplinar de 10 semanas para la pérdida de peso: programa EVASYON (www.estudioevasyon.org). Los adolescentes fueron genotipados para los 4 SNPs y tanto al comienzo como al final de la intervención se analizaron marcadores bioquímicos y se tomaron medidas antropométricas. RESULTADOS: Rs662799 del gen APOA5 se asoció al inicio con parámetros antropométricos y bioquímicos, mientras que el rs9939609 del gen FTO parecía estar asociado con el cambio de estas variables tras 10 semanas de intervención. Las variantes rs1800777 del gen CETP y rs670 del gen APOA1 mostraron una importante asociación con marcadores de adiposidad. Concretamente, un modelo combinado incluyendo los dos polimorfismos logró explicar hasta un 24% del cambio en el IMC-SDS tras 10 semanas de intervención. CONCLUSIÓN: Variantes genéticas previamente relacionadas con el metabolismo lipídico y energético, pueden repercutir no solamente en valores bioquímicos sino también en la respuesta a una intervención multidisciplinar para la pérdida de peso en adolescentes con sobrepeso u obesidad.

Telomere length as a biomarker for adiposity changes after a multidisciplinary intervention in overweight/obese adolescents: the EVASYON study.

CONTEXT: Telomeres are biomarkers of biological aging. Shorter telomeres have been associated with increased adiposity in adults. However, this relationship remains unclear in children and adolescents. OBJECTIVE: To evaluate the association between telomere length (TL) and adiposity markers in overweight/obese adolescents after an intensive program. We hypothesize that greater TL at baseline would predict a better response to a weight loss treatment. DESIGN SETTING PATIENTS AND INTERVENTION: The EVASYON is a multidisciplinary treatment program for adolescents with overweight and obesity that is aimed at applying the intervention to all possibly involved areas of the individual, such as dietary habits, physical activity and cognitive and psychological profiles. Seventy-four participants (36 males, 38 females, 12-16 yr) were enrolled in the intervention program: 2 months of an energy-restricted diet and a follow-up period (6 months). MAIN OUTCOME: TL was measured by quantitative real-time polymerase chain reaction at baseline and after 2 months; meanwhile, anthropometric variables were also assessed after 6 months of follow-up. RESULTS: TL lengthened in participants during the intensive period (+1.9±1.0, p<0.001) being greater in overweight/obese adolescents with the shortest telomeres at baseline (r = -0.962, p<0.001). Multivariable linear regression analysis showed that higher baseline TL significantly predicted a higher decrease in body weight (B = -1.53, p = 0.005; B = -2.25, p = 0.047) and in standard deviation score for body mass index (BMI-SDS) (B = -0.22, p = 0.010; B = -0.47, p = 0.005) after the intensive and extensive period treatment respectively, in boys. CONCLUSION: Our study shows that a weight loss intervention is accompanied by a significant increase in TL in overweight/obese adolescents. Moreover, we suggest that initial longer TL could be a potential predictor for a better weight loss response.

Differential DNA methylation patterns between high and low responders to a weight loss intervention in overweight or obese adolescents: the EVASYON study.

In recent years, epigenetic markers emerged as a new tool to understand the influence of lifestyle factors on obesity phenotypes. Adolescence is considered an important epigenetic window over a human's lifetime. The objective of this work was to explore baseline changes in DNA methylation that could be associated with a better weight loss response after a multidisciplinary intervention program in Spanish obese or overweight adolescents. Overweight or obese adolescents (n=107) undergoing 10 wk of a multidisciplinary intervention for weight loss were assigned as high or low responders to the treatment. A methylation microarray was performed to search for baseline epigenetic differences between the 2 groups (12 subjects/group), and MALDI-TOF mass spectrometry was used to validate (n=107) relevant CpG sites and surrounding regions. After validation, 5 regions located in or near AQP9, DUSP22, HIPK3, TNNT1, and TNNI3 genes showed differential methylation levels between high and low responders to the multidisciplinary weight loss intervention. Moreover, a calculated methylation score was significantly associated with changes in weight, BMI-SDS, and body fat mass loss after the treatment. In summary, we have identified 5 DNA regions that are differentially methylated depending on weight loss response. These methylation changes may help to better understand the weight loss response in obese adolescents.

Obesity susceptibility loci on body mass index and weight loss in Spanish adolescents after a lifestyle intervention.

OBJECTIVE: To estimate the contribution of 9 obesity-related polymorphisms and a genetic predisposition score (GPS) on anthropometric and biochemical variables before and after a weight loss intervention program in overweight/obese Spanish adolescents. STUDY DESIGN: Overweight/obese adolescents (n = 168; 12-16 years) participating in the EVASYON program were genotyped for 9 obesity-related single nucleotide polymorphisms in the FTO, MC4R, TMEM18, IL6, PPARG, and ADIPQ genes. RESULTS: At baseline, the GPS showed a significant association with body mass index-standard deviation score (BMI-SDS) and fat mass. After 3 months of intervention, this GPS also showed a relationship with the variation of both anthropometric measurements. After adjusting for baseline BMI-SDS, subjects with a lower GPS had a greater improvement on metabolic profile, as well as a better response to physical activity, compared with those subjects with a higher GPS. CONCLUSIONS: The GPS seems to have an important relationship with BMI-SDS and fat mass both at baseline and after a 3-month weight loss lifestyle intervention. Obese and overweight adolescents with a lower GPS have a greater benefit of weight loss after 3 months of a multidisciplinary lifestyle intervention.

Dietary fatty acid distribution modifies obesity risk linked to the rs9939609 polymorphism of the fat mass and obesity-associated gene in a Spanish case-control study of children.

The rs9939609 polymorphism of the fat mass and obesity-associated (FTO) gene has been widely associated with childhood obesity in several European cohorts. This association appears to be dependent on dietary macronutrients. Therefore, the aim of the present study was to evaluate whether dietary fatty acid intake distribution could interact with this FTO genetic variation and obesity in a Spanish case-control study of children and adolescents. A total of 354 Spanish children and adolescents aged 6-18 years (49 % males) were genotyped for the rs9939609 variant of the FTO gene. Anthropometric parameters were taken and energy intake was measured. We observed an interaction between the consumption of SFA (percentage of total energy) and PUFA:SFA ratio and obesity risk linked to the rs9939609 SNP of the FTO gene. In the study population of the present study, the risk allele carriers consuming more than 12·6 % SFA (of total energy) had an increased obesity risk compared with TT carriers. In a similar way, A allele carriers with an intake ratio lower than 0·43 PUFA:SFA presented a higher obesity risk than TT subjects. In summary, the present study reports for the first time the influence of dietary fatty acid distribution on the effect of the rs9939609 polymorphism of the FTO gene on children and adolescents' obesity risk.

Effects of the FTO gene on lifestyle intervention studies in children.

The effects of FTO on body weight, body composition, and the risk of developing overweight and obesity in children, adolescents, and adults are analyzed in this review. Most trails have been conducted on the rs9939609 SNP of the FTO gene. The minor A-allele frequency ranged from 0.38 to 0.49 in different European populations. Briefly, it has been reported that overweight-obesity risk per A-allele ranged from 1.76 to 1.35, whereas z-score for BMI has a wider variation from 0.05 to 0.5 kg/m(2) in European children and adolescents. As for other adiposity indexes, a waist circumference increase from 0.60 to 0.95 cm per A-allele was found together with an increase in fat mass from 0.68 to 1.78 kg in European children and adoles-cents. In regard to food intake, AA carrier subjects were reported to have reduced satiety responsiveness scores and a higher total energy and fat intake. However, it is not clear whether energy expenditure did modify the role of the rs9939609 FTO gene variant in adiposity. Furthermore, few reports examined the influence of FTO gene variants using intervention studies. Overall, it seems that the A-allele (rs9939609 FTO) is associated with higher body weight gain. However, further studies into FTO gene variants in children and adults are needed.