Telomere length and 4-year changes in cognitive function in an older Mediterranean population at high risk of cardiovascular disease.

BACKGROUND: Cognitive decline, a common process of brain ageing, has been associated with telomere length (TL). Delving into the identification of reliable biomarkers of brain ageing is essential to prevent accelerated cognitive impairment. METHODS: We selected 317 non-smoking 'Prevención con Dieta Mediterránea-Plus' (PREDIMED-Plus) participants (mean age, 65.8 ± 5.0 years) with metabolic syndrome from two trial centres who were following a lifestyle intervention. We measured TL and cognitive function at baseline and after 3 and 4 years of follow-up, respectively. Associations between baseline or 3-year changes in TL and baseline or 4-year changes in cognitive function were analysed using multivariable regression models. RESULTS: Baseline TL was not associated with baseline cognitive performance. Nevertheless, longer baseline TL was associated with improved 4-year changes in the Executive Function domain (ß: 0.29; 95%CI: 0.12 to 0.44; P < 0.001) and the Global Cognitive Function domain (ß: 0.19; 95%CI: 0.05 to 0.34; P = 0.010). Besides, a positive association was found between longer baseline TL and improved 4-year changes in the animal version of the Verbal Fluency Test (ß: 0.33; 95%CI: 0.12 to 0.52; P = 0.002). By contrast, 3-year changes in TL were not associated with changes in cognitive function after 4 years. CONCLUSIONS: Longer baseline TL could protect from cognitive decline and be used as a useful biomarker of brain ageing function in an older Mediterranean population at risk of cardiovascular disease and cognitive impairment.

Higher adherence to an empirically derived Mediterranean dietary pattern is positively associated with telomere length: the Seguimiento Universidad de Navarra (SUN) project.

Telomere integrity is influenced by oxidative stress. Also, inflammation-related factors, including nutritional factors, could modulate telomere integrity. The relationship between a posteriori-derived dietary patterns and telomere length (TL) has been scarcely investigated. Thus, our objective was to examine the association between empirically derived dietary patterns ascertained through principal component analysis (PCA) and TL in an older adult Spanish population. A total of 886 older adults (>55 years old; 645 males and 241 females) from the Seguimiento Universidad de Navarra (SUN) cohort were included in the study. TL was measured by monochrome multiplex real-time quantitative PCR. Age-adjusted TL was used for all analyses. Dietary patterns were identified by PCA based on thirty predefined candidate food groups collected from a validated 136-food items frequency questionnaire. Generalised linear models were fitted to obtain ß-coefficients and their 95 % CI evaluating differences in TL between each of the four upper quintiles of adherence to dietary patterns and the lowest quintile. Sensitivity analyses by rerunning all multiple linear models under different stratifications were performed to evaluate the robustness of our results. Two major dietary patterns were empirically identified, Western dietary pattern (WDP) and Mediterranean dietary pattern (MDP). After adjustment for potential confounders, longer TL was found among subjects in the highest quintile of MDP (ß = 0·064; 95 % CI 0·004, 0·123). The WDP showed no significant association with TL. In conclusion, higher adherence to a posteriori-derived MDP was independently associated with longer telomeres in an older adult Spanish population of the SUN project.

Associations of telomere length with anthropometric and glucose changes after a lifestyle intervention in abdominal obese children.

BACKGROUND AND AIMS: In lifestyle intervention studies, we demonstrated that changes in telomere length (TL) were associated with changes in anthropometric indices. Therefore, our new hypothesis is that TL could be a predictor of changes in anthropometric or metabolic measures in children with abdominal obesity. The aim of the study was to evaluate the association between anthropometric and biochemical measurements with TL before and after an 8-week lifestyle intervention in children with abdominal obesity (7-16 years old). METHODS AND RESULTS: We assessed anthropometric and biochemical outcomes at baseline and after 8-week lifestyle intervention in 106 children with abdominal obesity (11.30 ± 2.49 years old, 63% girls). TL was measured by monochrome multiplex real-time quantitative PCR. After the lifestyle intervention, anthropometric parameters and glucose metabolism indicators significantly improved in the participants. TL did not change after the intervention in participants. Significant negative correlations between baseline TL and anthropometric measures (BMI, body weight and waist circumference) were observed. Furthermore, baseline TL was a predictor for changes in blood glucose levels after the lifestyle intervention. CONCLUSIONS: An inverse correlation between TL and obesity traits was observed in children with abdominal obesity. Interestingly, we found that baseline TL could predict changes in blood glucose levels. CLINICAL TRIAL: NCT03147261. Registered 10 May 2017.

NADPH Oxidase Overactivity Underlies Telomere Shortening in Human Atherosclerosis.

Telomere shortening and oxidative stress are involved in the pathogenesis of atherosclerosis. Different studies have shown that phagocytic NADPH oxidase is associated with this disease. This study aimed to investigate the association between phagocytic NADPH oxidase and telomere shortening in human atherosclerosis. To assess this potential association, telomere length and phagocytic NADPH oxidase activity were determined by PCR and chemiluminescence, respectively, in a population of asymptomatic subjects free of overt clinical atherosclerosis. We also measured serum 8-hydroxy-2-deoxyguanosine (8-OHdG) levels (an index of oxidative stress) and carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis. After adjusting them for age and sex, telomere length inversely correlated (p < 0.05) with NADPH oxidase-mediated superoxide production, with 8-OHdG values, and with carotid IMT. Interestingly, the asymptomatic subjects with plaques have a lower telomere length (p < 0.05), and higher values of plasma 8-OHdG and superoxide production (p < 0.05). These data were confirmed in a second population in which patients with coronary artery disease showed lower telomere length and higher 8-OHdG and superoxide production than the asymptomatic subjects. In both studies, NADPH oxidase-dependent superoxide production in phagocytic cells was only due to the specific expression of the Nox2 isoform. In conclusion, these findings suggest that phagocytic NADPH oxidase may be involved in oxidative stress-mediated telomere shortening, and that this axis may be critically involved in human atherosclerosis.

Changes in objectively measured physical activity after a multidisciplinary lifestyle intervention in children with abdominal obesity: a randomized control trial.

BACKGROUND: Physical activity (PA) is associated with changes in body composition that affect insulin sensitivity and leptin levels. Few studies have assessed the effect of lifestyle interventions on changes in objectively measured PA levels in obese children. To evaluate the effects of a multidisciplinary lifestyle intervention on anthropometric indices, biochemical parameters and accelerometer measured PA in abdominal obese children. METHODS: A randomized control trial was performed in 106 children and adolescents with abdominal obesity. Participants were randomly assigned to usual or intensive care group for 8-week. PA was measured by accelerometry over four days including, at least, two weekdays in all participants. Both groups were encouraged to accumulate an extra time of 200 min per week in their PA. RESULTS: At baseline, 75% of subjects do not fulfill the WHO recommendation of being more than 60 min/day on moderate-to-vigorous PA (MVPA). The intensive care group achieved a significant reduction in anthropometric indexes compared to the usual care but no significant change was found in biochemical or PA parameters. Both groups achieved a significant reduction in light PA. Interestingly, intensive care participants significantly increased MVPA in 5.5 min/day. Moreover, an inverse association between changes in MVPA and leptin levels was found. CONCLUSION: The two lifestyle intervention reduced anthropometric indexes and lowered light PA in abdominal obese children. No significant differences were observed between intensive care and usual care in regard to PA. Intensive care participants significantly increase physical activity (MVPA) and, changes in MVPA were inversely associated with changes in leptin levels after the intervention. TRIAL REGISTRATION: ClinicalTrials.gov , Identifier: NCT03147261 . Registered 10 May 2017. Retrospectively registered.

Serum oxidized low-density lipoprotein levels are related to cardiometabolic risk and decreased after a weight loss treatment in obese children and adolescents.

BACKGROUND AND AIMS: The oxidation of low-density lipoprotein (LDL) cholesterol particles is an early atherogeninic event. Obese pediatric populations have higher levels of oxidized LDL (oxLDL) than normal weight children. The aim of this study was to evaluate the effect of a weight loss program on the biochemical profile and oxLDL levels in Spanish obese children and adolescents. METHODS: Forty obese children (mean age 11 years, 51% boys) followed a 10-week weight loss program. They were dichotomized at the median of body mass index-standard deviation score (BMI-SDS) change, as high (HR) and low responders (LR) after the intervention. The intervention included a moderate energy-restricted diet, nutritional education, and family involvement. Anthropometric and biochemical measurements were performed at the beginning and during the follow up. A cardiometabolic risk score (CMS) was calculated considering metabolic risk factors. RESULTS: Higher baseline oxLDL levels were associated with a higher CMS in obese children (P < .001). After the intervention, oxLDL significantly decreased in the HR group. Moreover, a positive correlation between changes in oxLDL and BMI-SDS (r = 0.385, P = .015) was found after the weight loss program. Interestingly, multiple-adjusted regression models showed an association between changes in total cholesterol [B: 0.127, 95% confidence interval (CI): 0.06 to 0.20] and LDL-cholesterol (B: 0.173, 95% CI: 0.08 to 0.26) with changes in oxLDL. CONCLUSIONS: Higher baseline oxLDL levels were associated with a higher CMS in obese children. After the weight loss program, a decrease in oxLDL levels was found in HR subjects and the oxLDL levels were associated with BMI-SDS and cholesterol levels.

Noncoding RNAs, cytokines, and inflammation-related diseases.

Chronic inflammation is involved in the onset and development of many diseases, including obesity, atherosclerosis, type 2 diabetes, osteoarthritis, autoimmune and degenerative diseases, asthma, periodontitis, and cirrhosis. The inflammation process is mediated by chemokines, cytokines, and different inflammatory cells. Although the molecules and mechanisms that regulate this primary defense mechanism are not fully understood, recent findings offer a putative role of noncoding RNAs, especially microRNAs (miRNAs), in the progression and management of the inflammatory response. These noncoding RNAs are crucial for the stability and maintenance of gene expression patterns that characterize some cell types, tissues, and biologic responses. Several miRNAs, such as miR-126, miR-132, miR-146, miR-155, and miR-221, have emerged as important transcriptional regulators of some inflammation-related mediators. Additionally, little is known about the involvement of long noncoding RNAs, long intergenic noncoding RNAs, and circular RNAs in inflammation-mediated processes and the homeostatic imbalance associated with metabolic disorders. These noncoding RNAs are emerging as biomarkers with diagnosis value, in prognosis protocols, or in the personalized treatment of inflammation-related alterations. In this context, this review summarizes findings in the field, highlighting those noncoding RNAs that regulate inflammation, with emphasis on recognized mediators such as TNF-α, IL-1, IL-6, IL-18, intercellular adhesion molecule 1, VCAM-1, and plasminogen activator inhibitor 1. The down-regulation or antagonism of the noncoding RNAs and the administration of exogenous miRNAs could be, in the near future, a promising therapeutic strategy in the treatment of inflammation-related diseases.

Association between dietary fibre intake and fruit, vegetable or whole-grain consumption and the risk of CVD: results from the PREvención con DIeta MEDiterránea (PREDIMED) trial.

Prospective studies assessing the association between fibre intake or fibre-rich food consumption and the risk of CVD have often been limited by baseline assessment of diet. Thus far, no study has used yearly repeated measurements of dietary changes during follow-up. Moreover, previous studies included healthy and selected participants who did not represent subjects at high cardiovascular risk. We used yearly repeated measurements of diet to investigate the association between fibre intake and CVD in a Mediterranean cohort of elderly adults at high cardiovascular risk. We followed-up 7216 men (55-80 years) and women (60-80 years) initially free of CVD for up to 7 years in the PREvención con DIeta MEDiterránea study (registered as ISRCTN35739639). A 137-item validated FFQ was repeated yearly to assess diet. The primary end point, confirmed by a blinded ad hoc Event Adjudication Committee, was a composite of cardiovascular death, myocardial infarction and stroke. Time-dependent Cox's regression models were used to estimate the risk of CVD according to baseline dietary exposures and to their yearly updated changes. We found a significant inverse association for fibre (P for trend=0·020) and fruits (P for trend=0·024) in age-sex adjusted models, but the statistical significance was lost in fully adjusted models. However, we found a significant inverse association with CVD incidence for the sum of fruit and vegetable consumption. Participants who consumed in total nine or more servings/d of fruits plus vegetables had a hazard ratio 0·60 (95 % CI 0·40, 0·96) of CVD in comparison with those consuming <5 servings/d.

Peripheral blood mononuclear cell gene expression profile in obese boys who followed a moderate energy-restricted diet: differences between high and low responders at baseline and after the intervention.

The present study analyses the gene expression profile of peripheral blood mononuclear cells (PBMC) from obese boys. The aims of the present study were to identify baseline differences between low responders (LR) and high responders (HR) after 10 weeks of a moderate energy-restricted dietary intervention, and to compare the gene expression profile between the baseline and the endpoint of the nutritional intervention. Spanish obese boys (age 10-14 years) were advised to follow a 10-week moderate energy-restricted diet. Participants were classified into two groups based on the association between the response to the nutritional intervention and the changes in BMI standard deviation score (BMI-SDS): HR group (n 6), who had a more decreased BMI-SDS; LR group (n 6), who either maintained or had an even increased BMI-SDS. The expression of 28,869 genes was analysed in PBMC from both groups at baseline and after the nutritional intervention, using the Affymetrix Human Gene 1.1 ST 24-Array plate microarray. At baseline, the HR group showed a lower expression of inflammation and immune response-related pathways, which suggests that the LR group could have a more developed pro-inflammatory phenotype. Concomitantly, LEPR and SIRPB1 genes were highly expressed in the LR group, indicating a tendency towards an impaired immune response and leptin resistance. Moreover, the moderate energy-restricted diet was able to down-regulate the inflammatory 'mitogen-activated protein kinase signalling pathway' in the HR group, as well as some inflammatory genes (AREG and TNFAIP3). The present study confirms that changes in the gene expression profile of PBMC in obese boys may help to understand the weight-loss response. However, further research is required to confirm these findings.

Association between yogurt consumption and the risk of metabolic syndrome over 6 years in the SUN study.

BACKGROUND: The role of yogurt consumption in the development of metabolic syndrome (MetS) is not fully understood and the available epidemiologic evidence is scarce. The aim of our study was to assess the association between total, whole-fat, or low-fat yogurt consumption and the risk of developing MetS. METHODS: Yogurt consumption was assessed at baseline through a 136-item validated FFQ. MetS was defined following the harmonized definition for MetS according to the AHA and the IDF criteria. Logistic regression models were used. RESULTS: During the first 6-y of follow-up of the SUN cohort, 306 incident cases of MetS were identified. Frequent consumption [≥875 g/week (≥7 servings/week) versus ≤ 250 g/week (2 servings/week)] of total, whole-fat and low-fat yogurt consumption showed non-significant inverse associations with MetS [OR = 0.84 (95% CI: 0.60-1.18); 0.98 (95% CI: 0.68-1.41); and 0.63 (95% CI: 0.39-1.02) respectively]. Only one component of the MetS, central adiposity, was inversely associated with total and whole-fat yogurt consumption [OR = 0.85 (95% CI: 0.74-0.98) and 0.85 (95% CI: 0.73-0.99) respectively]. In the joint assessment of exposure to total yogurt consumption and fruit consumption, those in the highest category of total yogurt consumption, and having a high fruit consumption (above the median ≥264.5 g/day) exhibited a significantly lower risk of developing MetS [OR = 0.61 (95% CI: 0.38-0.99)] compared with those in the lowest category of total yogurt consumption and had fruit consumption below the study median. CONCLUSION: No significant association between yogurt consumption and MetS was apparent. Only one component out of the 5 MetS criteria, central adiposity, was inversely associated with high yogurt consumption. The combination of high consumption of both yogurt and fruit was inversely associated with the development of MetS.

Novel association of the obesity risk-allele near Fas Apoptotic Inhibitory Molecule 2 (FAIM2) gene with heart rate and study of its effects on myocardial infarction in diabetic participants of the PREDIMED trial.

BACKGROUND: The Fas apoptotic pathway has been implicated in type 2 diabetes and cardiovascular disease. Although a polymorphism (rs7138803; G > A) near the Fas apoptotic inhibitory molecule 2 (FAIM2) locus has been related to obesity, its association with other cardiovascular risk factors and disease remains uncertain. METHODS: We analyzed the association between the FAIM2-rs7138803 polymorphism and obesity, blood pressure and heart rate in 7,161 participants (48.3% with type 2 diabetes) in the PREDIMED study at baseline. We also explored gene-diet interactions with adherence to the Mediterranean diet (MedDiet) and examined the effects of the polymorphism on cardiovascular disease incidence per diabetes status after a median 4.8-year dietary intervention (MedDiet versus control group) follow-up. RESULTS: We replicated the association between the FAIM2-rs7138803 polymorphism and greater obesity risk (OR: 1.08; 95% CI: 1.01-1.16; P = 0.011; per-A allele). Moreover, we detected novel associations of this polymorphism with higher diastolic blood pressure (DBP) and heart rate at baseline (B = 1.07; 95% CI: 0.97-1.28 bmp in AA vs G-carriers for the whole population), that remained statistically significant even after adjustment for body mass index (P = 0.012) and correction for multiple comparisons. This association was greater and statistically significant in type-2 diabetic subjects (B = 1.44: 95% CI: 0.23-2.56 bmp; P = 0.010 for AA versus G-carriers). Likewise, these findings were also observed longitudinally over 5-year follow-up. Nevertheless, we found no statistically significant gene-diet interactions with MedDiet for this trait. On analyzing myocardial infarction risk, we detected a nominally significant (P = 0.041) association in type-2 diabetic subjects (HR: 1.86; 95% CI:1.03-3.37 for AA versus G-carriers), although this association did not remain statistically significant following correction for multiple comparisons. CONCLUSIONS: We confirmed the FAIM2-rs7138803 relationship with obesity and identified novel and consistent associations with heart rate in particular in type 2 diabetic subjects. Furthermore, our results suggest a possible association of this polymorphism with higher myocardial infarction risk in type-2 diabetic subjects, although this result needs to be replicated as it could represent a false positive.

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.

Sugar-sweetened carbonated beverage consumption and childhood/adolescent obesity: a case-control study.

OBJECTIVE: To assess the association between the consumption of sugar-sweetened carbonated beverages (SSCB) and obesity in children and adolescents from Navarra (Spain). DESIGN: We used a matched case-control study design. The exposure, SSCB consumption (1 serving: 200 ml), was measured with a previously validated FFQ. Anthropometrical measures were taken using standardized protocols. The outcome, obesity, was defined as BMI above the age- and sex-specific 97th percentile according to the Spanish reference charts. In the analysis we used conditional logistic regression. Potential confounders were controlled using a multivariable model. SETTING: Subjects were recruited in the paediatric departments of the Universidad de Navarra Clinic and the Navarra Hospital Complex, and in three primary health centres of Navarra. Controls were recruited when attending for a routine medical examination or vaccination. SUBJECTS: One hundred and seventy-four obese children and 174 individually sex- and age-matched controls, 52·87% boys, with a mean age of 11·6 years. Exclusion criteria were dietary interventions, exposure to hormone treatment, development of secondary obesity due to endocrinopathy and serious intercurrent illness. RESULTS: Independently of other factors, high consumption of SSCB (>4 servings/week) was significantly associated with obesity (OR = 3·46; 95% CI 1·24, 9·62; P = 0·01). Besides, each additional daily serving of SSCB was associated with a 69% relative increase in the risk of obesity (OR = 1·69; 95% CI 1·04, 2·73; P = 0·03). CONCLUSIONS: We found a strong and significant association between SSCB consumption and obesity risk. Our results suggest a monotonic dose-response linear shape for this association in children and adolescents (P for trend = 0·02).

Effect of a 3-year lifestyle intervention on telomere length in participants from PREDIMED-Plus: A randomized trial.

BACKGROUND & AIMS: Short telomeres have been observed in chronic disease patients. Identifying environmental and lifestyle factors that could reduce telomere attrition is crucial for disease prevention. The aim of this work was to determine whether weight-loss induced by an energy-reduced Mediterranean diet (erMedDiet) and physical activity (PA) could modify telomere length (TL). METHODS: In 317 randomized non-smoker participants (mean age, 65.8 ± 4.98 years) with metabolic syndrome from two "Prevención con Dieta Mediterránea-Plus" (PREDIMED-Plus) trial centers, we evaluated MedDiet adherence, PA, anthropometric variables and TL at baseline and after a 3-year intervention using an intensive lifestyle program (IG) with an erMedDiet and PA or an unrestricted MedDiet without PA promotion (CG). RESULTS: Participants in the IG displayed greater 3-year weight reductions (-3.7 ± 4 kg, P < 0.001) compared to those in the CG. No differences in TL changes between groups were observed in the cohort as a whole. However, an interaction was observed between the intervention group and sex for TL changes (pinteraction = 0.039). Women in the IG showed an increase in TL after 3-y (+0.25 ± 0.9, relative units) compared to women in the CG (-0.07 ± 1.0) (pANCOVA = 0.036), whereas no differences between groups were observed in men. Women in the IG had a lower risk of telomere shortening after the intervention (OR = 0.17, 95%CI: 0.05-0.64, p = 0.008) compared to women in the CG. CONCLUSIONS: A 3-year lifestyle intervention based on an erMedDiet and PA slowed telomere shortening in women but not in men. TRIAL REGISTRATION: ISRCTN, ISRCTN89898870. Registered 24 July 2014- Retrospectively registered, https://www.isrctn.com/ISRCTN89898870.

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.

Circulating miRNAs in girls with abdominal obesity: miR-221-3p as a biomarker of response to weight loss interventions.

BACKGROUND: Recent studies have associated several microRNAs (miRNAs) with childhood obesity and energy homeostasis, suggesting that an individual miRNA profile could be used as an early predictor to estimate the response to weight loss interventions in the design of precision nutrition. OBJECTIVE: To investigate associations between the expression of circulating adiposity-related miRNAs and the response to a weight loss intervention. METHODS: A total of 51 Spanish girls (age 7-16 years) with abdominal obesity underwent 8 weeks of a multidisciplinary intervention for weight loss. Participants were stratified into two groups in accordance with changes in body mass index (BMI) standard deviation score: low-responders (LR) and high-responders (HR). The expression of 39 circulating miRNAs (c-miRNAs) was evaluated in plasma of all subjects before the intervention. RESULTS: Six miRNAs were differentially expressed between LR and HR. However, after adjustment for Tanner stage, the association was maintained only for miR-126-3p and miR-221-3p with a higher expression in HR group compared to LR group. After the intervention, miR-221-3p expression decreased in all subjects with a significant difference in the change within groups. However, changes in miR-126-3p levels were not significant. The expression of miR-221-3p was positively correlated with body weight, BMI and waist circumference, and negatively correlated with quantitative insulin sensitivity check index. CONCLUSIONS: Bioinformatic analysis evidenced that miR-221-3p participates in several obesity-related pathways, and more interestingly, this miRNA targets several candidate genes to childhood obesity according to DisGeNet database. Thus, miR-221-3p could be used for predicting the response to a multidisciplinary intervention for weight loss in young girls.

Dietary Exposure to Polychlorinated Biphenyls and Dioxins and Its Relationship to Telomere Length in Subjects Older Than 55 Years from the SUN Project.

Exposure to persistent organic pollutants (POPs) may influence telomere length (TL), which is considered as a marker of biological age associated with the risk of chronic disease. We hypothesized that dietary exposure to polychlorinated biphenyls (PCBs) and dioxins could affect TL. Our aim was to evaluate the association of dietary exposure to PCBs and dioxins with TL. In this cross-sectional study of 886 subjects older than 55 y (mean age: 67.7; standard deviation (SD): 6.1; 27% women) from the "Seguimiento Universidad de Navarra" (SUN) project. TL was determined by real-time quantitative polymerase chain reaction and dietary PCBs and dioxins exposure was collected using a validated 136-item Food Frequency Questionnaire. Multivariable linear regression models were used to control for potential confounding factors. Shorter TL was associated with dietary total PCBs (SD of T/S ratio/(ng/day) = -0.30 × 10-7; 95% CI, -0.55 × 10-7 to -0.06 × 10-7), dioxin-like PCBs (DL-PCBs) (SD of T/S ratio/(pg WHO TEQ (Toxic Equivalents)/day) = -6.17 × 10-7; 95% CI, -11.30 × 10-7 to -1.03 × 10-7), and total TEQ exposure (SD of T/S ratio/(pg WHO TEQ/day) = -5.02 × 10-7; 95% CI, -9.44 × 10-7 to -0.61 × 10-7), but not with dioxins (SD of T/S ratio/(pg WHO TEQ/day) = -13.90 × 10-7; 95% CI, -37.70 × 10-7 to 9.79 × 10-7). In this sample of middle-aged and older Spanish adults, dietary exposure to total PCBs and DL-PCBs alone and together with dioxins was associated with shorter TL. Further longitudinal studies, preferably with POPs measured in biological samples, are needed to confirm this finding.

Association between ideal cardiovascular health and telomere length in participants older than 55 years old from the SUN cohort.

INTRODUCTION AND OBJECTIVES: Telomeres are noncoding regions located at the end of chromosomes and their shortening has been associated with risk factors and cardiovascular disease. The aim of this study was to evaluate the association between ideal cardiovascular health (Life's simple 7) and the odds of having short telomeres in a subsample of participants older than 55 years from the Seguimiento Universidad de Navarra (SUN) study. METHODS: We included 886 participants older than 55 years (645 men and 241 women). Telomere length was measured using a real-time quantitative polymerase chain reaction. Cardiovascular health score was defined by the American Heart Association as a composite score of 7 key risk factors (smoking status, physical activity, diet, body mass index, blood pressure, total cholesterol, and fasting blood glucose) with 0 to 2 points for each factor. We categorized this score in tertiles as poor (0-9 points), intermediate (10-11 points) and ideal (12-14 points). The odds of having short telomeres was defined as telomere length below the 20th percentile. RESULTS: Individuals with higher ideal cardiovascular health had a lower prevalence of having short telomeres (adjusted OR, 0.60; 95%CI, 0.34-1.05; P trend=.052). This association was statistically significant in men (adjusted OR, 0.37; 95%CI, 0.17-0.83; P trend=.025) but not in women. CONCLUSIONS: An inverse association between cardiovascular health score and short telomeres was found especially for men older than 55 years in the SUN population. The SUN project was registered at ClinicalTrials.gov (Identifier: NCT02669602).

Determinants of Longitudinal Changes in Cardiometabolic Risk in Adolescents with Overweight/Obesity: The EVASYON Study.

We investigated which determinants (socioeconomic, early life factors, body composition changes, fitness changes and/or physical activity changes) best predicted longitudinal outcomes in cardiometabolic risk profile (Z-score change) in adolescents with OW/OB who underwent a 13-month multidisciplinary lifestyle intervention. A total of 165 adolescents (13-16 y; 46% boys) from the EVASYON study were included. Socioeconomic variables and early life factors were obtained from the medical records. Body composition was assessed using anthropometry. Fitness and physical activity were measured with field-based tests and questionnaires. Cardiometabolic risk factors (fasting glucose, HDL cholesterol, triglycerides, blood pressure and waist circumference) were derived from standard methods in the hospital. Body weight changes, sex and mother's education were selected in the stepwise process as the most important determinants of changes in cardiometabolic risk profile (R2 = 0.26, p = 0.002; R2 = 0.14, p = 0.013; and R2 = 0.14, p = 0.017, respectively). Both boys and girls showed a lower cardiometabolic risk score with the reduction in body weight (r = 0.535, p = 0.009 and r = 0.506, p = 0.005, respectively). There was no interaction between sex and body weight change (p = 0.614). In conclusion, the simple measure of changes in body weight should be considered to track changes in cardiometabolic risk profile in adolescents with OW/OB.