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- Changes in objectively measured physical activity after a multidisciplinary lifestyle intervention in children with abdominal obesity: a randomized control trial(Springer Science and Business Media LLC, 2019) Martin-Calvo, N. (Nerea); Ochotorena-Elicegui, A. (Amaia); Azcona-San-Julian, M.C. (María Cristina); Ojeda-Rodríguez, A. (Ana); Chueca, M. (María); Morell-Azanza, L. (Lydia); Marti-del-Moral, A. (Amelia)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.
- Improved diet quality and nutrient adequacy in children and adolescents with abdominal obesity after a lifestyle intervention(MDPI AG, 2018) Chueca-Guindulain, M.J. (María Jesús); Zazpe, I. (Itziar); Azcona-San-Julian, M.C. (María Cristina); Ojeda-Rodríguez, A. (Ana); Morell-Azanza, L. (Lydia); Marti-del-Moral, A. (Amelia)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.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.
- Melanocortin-4 Receptor and Lipocalin 2 Gene Variants in Spanish Children with Abdominal Obesity: Effects on BMI-SDS after a Lifestyle Intervention(MDPI AG, 2019) Hinney, A. (Anke); Hebebrand, J. (Joahnnes); Giuranna, J. (Johanna); Azcona-San-Julian, M.C. (María Cristina); Ojeda-Rodríguez, A. (Ana); Morell-Azanza, L. (Lydia); Marti-del-Moral, A. (Amelia)Mutations leading to a reduced function of the melanocortin-4 receptor (MC4R) exert a major gene effect on extreme obesity. Recently it was shown that the bone derived hormone lipocalin 2 (LCN2) binds to the MC4R and activates a MC4R dependent anorexigenic pathway. We identified mutations in both genes and screened the effects of MC4R and LCN2 mutations on eating behavior and weight change after a lifestyle intervention. One hundred and twelve children (11.24 ± 2.6 years, BMI-SDS 2.91 ± 1.07) with abdominal obesity participated in a lifestyle intervention. MC4R and LCN2 coding regions were screened by Sanger sequencing. Eating behavior was assessed at baseline with the Children Eating Behavior Questionnaire (CEBQ). We detected three previously described non-synonymous MC4R variants (Glu42Lys, Thr150Ile, and Arg305Gln) and one non-synonymous polymorphism (Ile251Leu). Regarding LCN2, one known non-synonymous variant (Thr124Met) was detected. Eating behavior was described in carriers of the MC4R and LCN2 mutation and in non-carriers. MC4R and LCN2 mutations were detected in 2.42% and 0.84%, respectively, of Spanish children with abdominal obesity. A number of subjects with functional mutation variants in MC4R and LCN2 were able to achieve a reduction in BMI-SDS after a lifestyle intervention.
- Cardiometabolic risk after two lifestyle interventions in children with obesity: the role of genetic markers(2019-07-15) Morell-Azanza, L. (Lydia); Azcona-San-Julian, M.C. (María Cristina); Marti-del-Moral, A. (Amelia)Childhood obesity has increased in recent years. In Spain about one in four children are overweight or obese, and most of them will carry this status into adulthood. Health consequences derived from obesity are numerous and complex, but the most frequent are those related to cardiometabolic risk and the future development of type 2 diabetes mellitus and cardiovascular disease. Different strategies have been proposed to reduce adiposity and improve metabolic outcomes in children with obesity. Lifestyle interventions that combined dietary, physical activity and behavioural approaches with family involvement appear to be the best options to prevent weight regain. Since, obesity development stands from the interplay between lifestyle and genetic factors it is important to understand how genetic markers could influence the weight loss response. Thus, the general objective of the present project is to evaluate the effect of two lifestyle interventions on cardiometabolic risk in children with obesity. The role of genetic markers in the individual response to the intervention will also be evaluated. This thesis project includes two different lifestyle programs: 1) the NUGENOI study based on a dietary intensive intervention (10 weeks), and 2) the IGENOI study, an integral intervention with a 2-year duration (2 months + 22 months of follow up). Both lifestyle interventions were able to reduce adiposity and improve metabolic outcomes. Parameters related to cardiometabolic risk such as inflammatory cytokines and oxidized LDL cholesterol were also diminished in children with obesity. In addition, changes in glucose metabolism derived from the lifestyle intervention were associated with cardiotrophin-1 gene expression at baseline. The integral intervention of IGENOI study includes the promotion of physical activity in children. Concerning this, children with abdominal obesity from the intensive care group were more physically active (+5.5 minutes of daily increase in moderate-to-vigorous physical activity assessed by accelerometry) and lowered their cardiometabolic risk after the intervention. In fact, favorable changes in MVPA were related to changes in leptin levels. Telomere length is influenced by oxidative stress and inflammatory status, these two processes are present in obese subjects. We observed inverse associations between telomere length and adiposity indices. Moreover, baseline telomere length seemed to be a marker of changes in glucose levels. Moreover, no change in TL was observed, despite achieving a successful decrease in BMI-SDS after the integral lifestyle intervention. Finally, IGENOI participants were screened for functional mutations in Melanocortin 4 Receptor (MC4R) and Lipocalin 2 (LCN2) genes. The prevalence for the two gene variants were 2.42% and 0.84% for MC4R and LCN2, respectively. These genetic variants seem to partially explain eating behaviours. Nevertheless, subjects with those functional mutations were able to decrease adiposity after our integral lifestyle intervention. In summary, lifestyle interventions conducted in children with obesity were effective in the reduction of adiposity and metabolic outcomes. It appears that telomere length and cardiotrophin-1 gene expression could have a predictive role in glucose metabolism outcomes. Meanwhile, MC4R and LCN2 mutations could influence eating behaviours but did not change the weight loss response.
- Pistachio consumption modulates DNA oxidation and genes related to telomere maintenance: a crossover randomized clinical trial(Oxford University Press (OUP), 2019) Galié, S. (Serena); Canudas, Silvia (S.); García-Gavilán, J.F. (Jesús F.); Hernandez-Alonso, P. (Pablo); Muralidharan, J. (Jananee); Bullo, M. (Monica); Zalba, G. (Guillermo); Salas-Salvado, J. (Jordi); Morell-Azanza, L. (Lydia); Marti-del-Moral, A. (Amelia)Background: Telomere attrition may play an important role in the pathogenesis and severity of type 2 diabetes (T2D), increasing the probability of β cell senescence and leading to reduced cell mass and decreased insulin secretion. Nutrition and lifestyle are known factors modulating the aging process and insulin resistance/secretion, determining the risk of T2D. Objectives: The aim of this study was to evaluate the effects of pistachio intake on telomere length and other cellular aging-related parameters of glucose and insulin metabolism. Methods: Forty-nine prediabetic subjects were included in a randomized crossover clinical trial. Subjects consumed a pistachio-supplemented diet (PD, 50 E% [energy percentage] carbohydrates and 33 E% fat, including 57 g pistachios/d) and an isocaloric control diet (CD, 55 E% carbohydrates and 30 E% fat) for 4 mo each, separated by a 2-wk washout period. DNA oxidation was evaluated by DNA damage (via 8-hydroxydeoxyguanosine). Leucocyte telomere length and gene expression related to either oxidation, telomere maintenance or glucose, and insulin metabolism were analyzed by multiplexed quantitative reverse transcriptase-polymerase chain reaction after the dietary intervention. Results: Compared with the CD, the PD reduced oxidative damage to DNA (mean: -3.5%; 95% CI: -8.07%, 1.05%; P = 0.009). Gene expression of 2 telomere-related genes (TERT and WRAP53) was significantly upregulated (164% and 53%) after the PD compared with the CD (P = 0.043 and P = 0.001, respectively). Interestingly, changes in TERT expression were negatively correlated to changes in fasting plasma glucose concentrations and in the homeostatic model assessment of insulin resistance. Conclusions: Chronic pistachio consumption reduces oxidative damage to DNA and increases the gene expression of some telomere-associated genes. Lessening oxidative damage to DNA and telomerase expression through diet may represent an intriguing way to promote healthspan in humans, reversing certain deleterious metabolic consequences of prediabetes.