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.

Telomere Length and Pediatric Obesity: A Review.

Obesity is a chronic disease, which needs to be early detected early and treated in order prevent its complications. Changes in telomere length (TL) have been associated with obesity and its complications, such as diabetes mellitus and metabolic syndrome. Therefore, we conducted a systematic review to summarize results of studies that have measured TL in children and adolescents with obesity. Fourteen studies aiming to assess TL in pediatric patients with either obesity or who were overweight were included in this review. In conclusion, obesity and adiposity parameters are negatively associated with TL. Shorter telomeres are observed in children with obesity compared with their lean counterparts. Factors involved in obesity etiology, such as diet and physical activity, may contribute to maintenance of TL integrity. In the long term, TL change could be used as a biomarker to predict response to obesity treatment.

Higher Lipopolysaccharide Binding Protein and Chemerin Concentrations Were Associated with Metabolic Syndrome Features in Pediatric Subjects with Abdominal Obesity during a Lifestyle Intervention.

Elevated circulating plasma levels of both lipopolysaccharide-binding protein (LBP) and chemerin are reported in patients with obesity, but few studies are available on lifestyle intervention programs. We investigated the association of both LBP and chemerin plasma levels with metabolic syndrome (MetS) outcomes in a lifestyle intervention in children and adolescents with abdominal obesity Methods: Twenty-nine patients enrolled in a randomized controlled trial were selected. The lifestyle intervention with a 2-month intensive phase and a subsequent 10-month follow-up consisted of a moderate calorie-restricted diet, recommendations to increase physical activity levels, and nutritional education. Results: Weight loss was accompanied by a significant reduction in MetS prevalence (-43%; p = 0.009). Chemerin (p = 0.029) and LBP (p = 0.033) plasma levels were significantly reduced at 2 months and 12 months, respectively. At the end of intervention, MetS components were associated with both LBP (p = 0.017) and chemerin (p < 0.001) plasma levels. Conclusions: We describe for the first time a reduction in both LBP and chemerin plasma levels and its association with MetS risk factors after a lifestyle intervention program in children and adolescents with abdominal obesity. Therefore, LBP and chemerin plasma levels could be used as biomarkers for the progression of cardiovascular risk in pediatric populations.

Association between favourable changes in objectively measured physical activity and telomere length after a lifestyle intervention in pediatric patients with abdominal obesity.

The purpose of this study was to assess the effect of physical activity (PA) changes, measured by accelerometry, on telomere length (TL) in pediatric patients with abdominal obesity after a lifestyle intervention. One hundred and twenty-one children (7-16 years old) with abdominal obesity were randomized to the intervention (a moderately hypocaloric Mediterranean diet) or the usual care group (standard pediatric recommendations) for 22 months (a 2 month intensive phase and a subsequent 20 month follow-up). Both groups were encouraged to accumulate an extra 200 min/week of PA. TL was measured by MMqPCR. Data were analyzed in 102 subjects after 2 months and 64 subjects at the first 10 months of follow-up. Light PA level decreased in both groups after 12 months of intervention. At month 2, moderate to vigorous PA (MVPA) increased in the intervention group (+5.4 min/day, p = 0.035) and so did sedentary time in the usual care group (+49.7 min/day, p = 0.010). TL changes were positively associated (p < 0.050) with metabolic equivalents (METs), MVPA level, and number of steps, and were inversely associated with sedentary and light PA levels in the intervention group after the intensive phase. In conclusion, favourable changes in PA levels in the intensive phase of a lifestyle intervention could contribute to TL maintenance in a pediatric population with abdominal obesity. Novelty Changes in physical activity levels had a direct effect on telomere length, a biomarker of cellular aging and oxidative stress. PA advice based on The American College of Sports Medicine included in this intervention is easy to implement in primary care.

Associations of telomere length with two dietary quality indices after a lifestyle intervention in children with abdominal obesity: a randomized controlled trial.

BACKGROUND: Dietary factors seem to influence telomere length. Moreover, associations between changes in adiposity indices and telomere length (TL) have been found in intervention studies. OBJECTIVE: We evaluated changes in two diet quality indices and their association with TL in children with abdominal obesity in a 12-month lifestyle intervention. METHODS: Eighty-seven participants (7-16 years old) were assigned to the intervention (moderate hypocaloric Mediterranean diet) or usual care group (standard paediatric recommendations) for a 2-month intensive phase and a subsequent 10-month follow-up. Diet quality was assessed using the Diet Quality Index for Adolescents (DQI-A) and the Healthy Lifestyle Diet Index (HLD-I). TL was measured by monochrome multiplex real-time quantitative PCR. The intra-class correlation coefficient for TL was 0.793 (95% CI 0.707, 0.857). RESULTS: After a 12-month lifestyle intervention, a significant reduction in BMI-SDS (-0.57 and -0.49 for the intervention and usual care groups, respectively) and fat mass was observed in all subjects without differences between groups. Changes in DQI-A (+12.36% vs +5.53%, P = .005) and HLD-I (+4.43 vs +1.09, P < .001) were higher in the intervention subjects compared with usual care subjects after 2 months. Interestingly, we observed a positive change in TL between 2 and 12 months (P = .025), which was associated with higher scores on the DQI-A (ß = 0.008, R2 = 0.088, P = .010) and HLD-I (ß = 0.022, R2 = 0.198, P = .015), in the intervention group after the 2-month intensive phase. CONCLUSION: Favourable changes in diet quality indices could contribute to telomere integrity in children with abdominal obesity enrolled in an intensive lifestyle intervention.

Improved Diet Quality and Nutrient Adequacy in Children and Adolescents with Abdominal Obesity after a Lifestyle Intervention.

High rates of childhood obesity require integral treatment with lifestyle modifications that achieve weight loss. We evaluated a lifestyle intervention on nutrient adequacy and diet quality in children and adolescents with abdominal obesity. A randomized controlled trial was performed on 107 participants, assigned either to a usual care group or to an intensive care group that followed a moderate hypocaloric Mediterranean diet and received nutritional education. Intake adequacy was evaluated using Dietary Reference Intakes and diet quality through the Diet Quality Index for Adolescents (DQI-A), the Healthy Lifestyle Diet-Index (HLD-I) and the Mediterranean Diet Quality Index (KIDMED). Both groups achieved a significant reduction in BMI standard deviation score (BMI-SDS), glucose and total cholesterol levels. Intake of Calcium, Iodine and vitamin D were higher in the intensive care group, with enhanced compliance with recommendations. Higher dietary scores were associated with lower micronutrient inadequacy. DQI-A and HLD-I were significantly higher in the intensive care group vs. usual care group after the treatment. In conclusion, we observed that an intensive lifestyle intervention was able to reduce BMI-SDS in children with abdominal obesity. Furthermore, participants significantly improved dietary indices getting closer to the nutritional recommendations. Therefore, these diet quality indices could be a valid indicator to evaluate micronutrient adequacy.

Reduced serotonin levels after a lifestyle intervention in obese children: association with glucose and anthropometric measurements.

BACKGROUND: serotonin signaling participates in body weight regulation and glucose metabolism. However, little information is available on circulating serotonin levels in obese subjects after a weight loss program. We aimed to assess the effect of a lifestyle intervention on serotonin levels in obese children and possible associations with anthropometric and blood glucose measurements. METHODS: forty-four obese children were enrolled in a ten-week lifestyle intervention consisting of a moderate caloric restriction diet, nutritional education and familial involvement. They were distributed according to the weight loss response. Subjects who lost > 0.5 BMI-SDS were considered as high responders (HR; n = 22) and those who lost ≤ 0.5 BMI-SDS, as low responders (LR; n = 22). Anthropometric, biochemical parameters and plasma serotonin levels were measured as pre and post-intervention values. RESULTS: obese children (HR and LR groups) were able to reduce anthropometric indices and to improve glucose profile after the intervention. Interestingly, plasma serotonin levels were significantly (p ˂0.05) reduced in all subjects (-35.14 nmol/l HR group and -30.63 nmol/l LR group). Moreover, multiple-adjusted regression models showed a significant association between pre-intervention (R2 = 0.224, B = 0.047; p = 0.004) and post-intervention (R2 = 0.140; B = 0.055; p = 0.042) plasma serotonin and glucose levels. In addition, in HR subjects changes in plasma serotonin were associated with changes in glucose levels (R2 = 0.292; b = 0.04; p = 0.045). Interestingly, pre and post-intervention plasma serotonin levels were inversely associated (p ˂0.05) with anthropometric measures. CONCLUSIONS: serotonin levels were reduced after a lifestyle intervention independently of the program response. Moreover, plasma serotonin levels were associated with glucose and anthropometric measures in obese children.

Reduced serotonin levels after a lifestyle intervention in obese children: association with glucose and anthropometric measurements / Disminución de los niveles de serotonina tras una intervención de estilo de vida en niños obesos: asociación con glucosa y medidas antropométricas

Background: serotonin signaling participates in body weight regulation and glucose metabolism. However, little information is available on circulating serotonin levels in obese subjects after a weight loss program. We aimed to assess the effect of a lifestyle intervention on serotonin levels in obese children and possible associations with anthropometric and blood glucose measurements. Methods: forty-four obese children were enrolled in a ten-week lifestyle intervention consisting of a moderate caloric restriction diet, nutritional education and familial involvement. They were distributed according to the weight loss response. Subjects who lost >0.5 BMI-SDS were considered as high responders (HR; n = 22) and those who lost ≤ 0.5 BMI-SDS, as low responders (LR; n = 22). Anthropometric, biochemical parameters and plasma serotonin levels were measured as pre and post-intervention values. Results: obese children (HR and LR groups) were able to reduce anthropometric indices and to improve glucose profile after the intervention. Interestingly, plasma serotonin levels were significantly (p <0.05) reduced in all subjects (-35.14 nmol/l HR group and -30.63 nmol/l LR group). Moreover, multiple-adjusted regression models showed a significant association between pre-intervention (R2 = 0.224, B = 0.047; p = 0.004) and post-intervention (R2 = 0.140; B = 0.055; p = 0.042) plasma serotonin and glucose levels. In addition, in HR subjects changes in plasma serotonin were associated with changes in glucose levels (R2 = 0.292; b = 0.04; p = 0.045). Interestingly, pre and post-intervention plasma serotonin levels were inversely associated (p <0.05) with anthropometric measures. Conclusions: serotonin levels were reduced after a lifestyle intervention independently of the program response. Moreover, plasma serotonin levels were associated with glucose and anthropometric measures in obese children

Introducción: la señalización de la serotonina está involucrada en la regulación del peso corporal y el metabolismo de la glucosa. Sin embargo, existe poca información disponible sobre los niveles de serotonina circulantes en sujetos obesos tras un programa de pérdida de peso. Nuestro objetivo fue evaluar el efecto de una intervención de estilo de vida en los niveles plasmáticos de serotonina en niños obesos y su posible asociación con medidas antropométricas y de glucosa en sangre. Métodos: cuarenta y cuatro niños obesos participaron en una intervención de estilo de vida durante diez semanas consistente en una dieta con restricción calórica moderada, educación nutricional y participación familiar. Los sujetos que perdieron >0,5 z-IMC fueron considerados como altos respondedores (AR; n = 22) y aquellos que perdieron ≤ 0,5 z-IMC, como bajos respondedores (BR; n = 22). Los parámetros antropométricos y bioquímicos y los niveles plasmáticos de serotonina se midieron antes y después de la intervención. Resultados: los niños obesos (grupos AR y BR) pudieron reducir los índices antropométricos y mejorar el perfil lipídico y glucémico tras la intervención. Los niveles plasmáticos de serotonina fueron significativamente (p <0,05) reducidos en todos los sujetos (-35,14 nmol/l grupo de AR y -30,63 nmol/l grupo de BR). Por otra parte, los modelos de regresión múltiple ajustada mostraron una asociación significativa entre los niveles plasmáticos de serotonina y glucosa previos a la intervención (R2 = 0,224; B = 0,047; p = 0,004) y tras la intervención (R2 = 0,140; B = 0,055; p = 0,042). Además, en los sujetos AR los cambios en la serotonina plasmática se asociaron con cambios en los niveles de glucosa (R2 = 0,292; b = 0,04; p = 0,045). Los niveles de serotonina plasmática antes y después de la intervención se asociaron inversamente (p <0,05) con índices antropométricos. Conclusiones: los niveles plasmáticos de serotonina se redujeron tras una intervención de estilo de vida en todos los grupos. Además, los niveles plasmáticos de serotonina se asociaron con niveles de glucosa e índices antropométricos en niños obesos

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.

Decreased cardiotrophin-1 levels are associated with a lower risk of developing the metabolic syndrome in overweight/obese children after a weight loss program.

OBJECTIVE: Cardiotrophin-1 (CT-1) shares some similarities with other cytokines, and participates in the control of energy metabolism. Higher circulating levels are observed in obese humans, but little information is gathered in weight loss (WL) programs. Therefore, we aimed to investigate the association of serum CT-1 levels with metabolic variables and the risk of developing metabolic syndrome (MetS) after a WL program in overweight/obese children. SUBJECTS AND METHODS: Forty-four overweight/obese children (mean age 11.5 y; 50% males) undergoing a 10-week WL program were enrolled. Subjects were dichotomized at the median of Body Mass Index-Standard Deviation Score (BMI-SDS) change, as high and low responders after intervention. RESULTS: CT-1 levels were significantly reduced (-48 fmol/mL, p=0.043) in the high responder group after the WL program. They had significantly lower body weight (-3.7 kg, p<0.001), body fat mass (-8%, p<0.001), BMI-SDS (-0.78, p<0.001) and waist circumference (-5.4 cm, p<0.001), and a significant improvement in lipid and glucose profiles (p<0.05). Interestingly, decreased CT-1 levels significantly predicted changes in total cholesterol (41%) and LDL-cholesterol (28%). Moreover, in our participants the lower the CT-1 levels, the higher the reduction in MetS risk components, after the 10-week intervention, (p-ANCOVA=0.040, p-trend=0.024). CONCLUSION: We showed, for the first time, a reduction in serum CT-1 levels after a WL program and this decrease in CT-1 was strongly associated with a reduction in cholesterol levels and in MetS risk factors in overweight/obese children. Our findings may suggest that CT-1 could be an indirect marker for the diagnosis of MetS in this population.