Circulating miRNAs as Biomarkers of Obesity and Obesity-Associated Comorbidities in Children and Adolescents: A Systematic Review

Early detection of obesity and its associated comorbidities in children needs priority for the development of effective therapeutic intervention. Circulating miRNAs (microRNAs) have been proposed as biomarkers for obesity and its comorbidities; therefore, we conducted a systematic review to summarize results of studies that have quantified the profile of miRNAs in children and adolescents with obesity and/or associated disorders. Nine studies aiming to examine differences in miRNA expression levels between children with normal weight and obesity or between obese children with or without cardiometabolic diseases were included in this review. We identified four miRNAs overexpressed in obesity (miR-222, miR-142–3, miR-140-5p, and miR-143) and two miRNAs (miR-122 and miR-34a) overexpressed in children with obesity and nonalcoholic fatty liver disease (NAFLD) and/or insulin resistance. In conclusion, circulating miRNAs are promising diagnostic biomarkers of obesity-associated diseases such as NAFLD and type 2 diabetes already in childhood. However, more studies in children, using massive search technology and with larger sample sizes, are required to draw any firm conclusions.This research was funded by the Spanish Ministry of Industry and Competitiveness (DEP2016-78377-R) and by the European Regional Development Fund (ERDF), M.O. is supported by a grant from the Spanish Ministry of Economy and Competitiveness, grant number; BES-2017-080770 and the APC was funded by additional support from the University of Granada, UGR Research and Knowledge Transfer Fund (PPIT) 2016, Excellence Actions Programme, and Excellence Actions Programe. C.M.A. and I.L.G. are part of the “URG Plan propio de Investigación 2016” and the “Excellence actions: Unit of Excellence on Exercise and Health (UCEES), University of Granada

The Effect of a Family-Based Lifestyle Education Program on Dietary Habits, Hepatic Fat and Adiposity Markers in 8–12-Year-Old Children with Overweight/Obesity

Healthy lifestyle education programs are recommended for obesity prevention and treatment. However, there is no previous information on the effects of these programs on the reduction of hepatic fat percentage. The aims were (i) to examine the effectiveness of a 22-week family-based lifestyle education program on dietary habits, and (ii) to explore the associations of changes in dietary intake with percent hepatic fat reduction and adiposity in children with overweight/obesity. A total of 81 children with overweight/obesity (aged 10.6 ± 1.1 years, 53.1% girls) and their parents attended a 22-week family based healthy lifestyle and psychoeducational program accompanied with (intensive group) or without (control) an exercise program. Hepatic fat (magnetic resonance imaging), adiposity (dual energy X-ray absorptiometry) and dietary habits (two non-consecutive 24 h-recalls) were assessed before and after the intervention. Energy (p < 0.01) fat (p < 0.01) and added sugar (p < 0.03) intake were significantly reduced in both groups at the end of the program, while, in addition, carbohydrates intake (p < 0.04) was reduced exclusively in the control group, and simple sugar (p < 0.05) and cholesterol (p < 0.03) intake was reduced in the exercise group. Fruit (p < 0.03) and low-fat/skimmed dairy consumption (p < 0.02), the adherence to the Mediterranean Diet Quality Index for children and teenagers (KIDMED, p < 0.01) and breakfast quality index (p < 0.03) were significantly higher in both control and intervention groups after the intervention. Moreover, participants in the exercise group increased the adherence to the Dietary Approaches to Stop Hypertension (DASH) diet (p < 0.001), whereas the ratio of evening-morning energy intake was significantly lower exclusively in the control group after the program (p < 0.02). Changes in energy intake were significantly associated with changes in fat mass index (FMI) in the exercise group, whereas changes in sugar-sweetened beverages (SSB) consumption was associated with percent hepatic fat reduction (p < 0.05) in the control group. A 22-week family-based healthy lifestyle program seems to be effective on improving diet quality and health in children with overweight/obesity and these should focus on SSB avoidance and physical activity.The current project was supported by the Spanish Ministry of Industry and Competitiveness (DEP2016-78377-R), by European Regional Development Funds (ERDF) and by the University of the Basque Country (GIU14/21). This work was also supported by grants from Spanish Ministry of Economy and Competitiveness (RYC 2010-05957; RYC-2011-09011; BES-2017-080770), by the Education Department of the Government of the Basque Country (PRE_2016_1_0057, PRE_2017_2_0224, PRE_2018_2_0057, PRE_2019_2_0004) and by the University of the Basque Country (PIF17/186). This study has been partially funded by the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and by ERDF, (ref. SOMM17/6107/UGR)

Influence of Physical Activity on Bone Mineral Content and Density in Overweight and Obese Children with Low Adherence to the Mediterranean Dietary Pattern.

The objective of the present cross-sectional study was to examine the associations of physical activity and the adherence to the Mediterranean dietary pattern (MDP) with bone mineral content (BMC) and density (BMD) in children with overweight and obesity. A total of 177 (n = 80 girls) children with overweight and obesity aged 8 to 12 years old participated in the study. Both BMC and BMD were assessed by Dual-Energy X-ray absorptiometry. Dietary patterns were assessed by the KIDMED questionnaire and two 24-hour recalls. Physical activity was assessed by accelerometers for 7 consecutive days (24 hours/day). Low adherence to the MDP was observed in 82.4% of participants. Higher physical activity levels (of at least moderate intensity) and lower sedentary time were significantly associated with BMC and BMD in children with low adherence to the MDP (all p < 0.05). No associations were observed between physical activity and BMC and BMD in children with high adherence to the MDP. In conclusion, engaging in moderate to vigorous physical activity and reducing the time spent in sedentary behavior might be particularly beneficial for improving bone health in overweight or obese children with poor adherence to the Mediterranean dietary pattern.The ActiveBrains Project was funded by the Spanish Ministry of Economy and Competitiveness (Reference DEP2013-47540 and DEP2016-79512-R). EFIGRO was supported by the Spanish Ministry of Health, “Fondo de Investigación Sanitaria del Instituto de Salud Carlos III” (PI13/01335), “Fondos Estructurales de la Unión Europea (FEDER), Una manera de hacer Europa”, by the University of the Basque Country (GIU14/21), and by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). LGM is funded by Programa de Captación de Talento-UGR Fellows. MM is supported by grant from the Spanish Ministry of Education, Culture and Sport (FPU14/03329) and EST17/00210. LA is supported by a grant from Education, Linguistic Policy, and Culture Department of the Government of the Basque Country (PRE_2016_1_0057)

Differences in areal bone mineral density between metabolically healthy and unhealthy overweight/obese children: the role of physical activity and cardiorespiratory fitness

“This manuscript was published by SPRINGERNATURE in Pediatric Research on June 2020, available at: doi: 10.1038/s41390-019-0708-x.”OBJECTIVES: To examine whether areal bone mineral density (aBMD) differs between metabolically healthy (MHO) and unhealthy (MUO) overweight/obese children and to examine the role of moderate-to-vigorous physical activity (MVPA) and cardiorespiratory fitness (CRF) in this association. METHODS: A cross-sectional study was developed in 188 overweight/obese children (10.4 ± 1.2 years) from the ActiveBrains and EFIGRO studies. Participants were classified as MHO or MUO based on Jolliffe and Janssen’s metabolic syndrome cut-off points for triglycerides, glucose, high-density cholesterol and blood pressure. MVPA and CRF were assessed by accelerometry and the 20-m shuttle run test, respectively. Body composition was measured by dual-energy X-ray absorptiometry. RESULTS: In model 1 (adjusted for sex, years from peak high velocity, stature and lean mass), MHO children had significantly higher aBMD in total body less head (Cohen’s d effect size, ES = 0.34), trunk (ES = 0.43) and pelvis (ES = 0.33) than MUO children. These differences were attenuated once MVPA was added to model 1 (model 2), and most of them disappeared once CRF was added to the model 1 (model 3). CONCLUSIONS: This novel research shows that MHO children have greater aBMD than their MUO peers. Furthermore, both MVPA and more importantly CRF seem to partially explain these findings.The authors thank the staff and participants of the ActiveBrains and EFIGRO studies for their important contributions. This study has been partially funded by the University of Granada, UGR Research and Knowledge Transfer Fund (PPIT) 2016, Excellence Actions Programme: Units of Scientific Excellence; Scientific Unit of Excellence on Exercise and Health (UCEES), and by the Regional Government of Andalusia, Regional Ministry of Economy, Knowledge, Enterprises and University and European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR. The ActiveBrains study was funded by the Spanish Ministry of Economy and Competitiveness (Reference DEP2013-47540, DEP2016-79512-R, and DEP2017-91544-EXP). The EFIGRO study was funded by the Spanish Ministry of Health, “Fondo de Investigación Sanitaria del Instituto de Salud Carlos III” (PI13/01335), “Fondos Estructurales de la Unión Europea (FEDER), Una manera de hacer Europa,” and by the University of the Basque Country (GIU14/21). L.G.-M. is supported by “La Caixa” Foundation within the Junior Leader fellowship programme (ID 100010434); M.M. is supported by the Spanish Ministry of Education, Culture and Sport (FPU14/03329) and EST17/00210; L.A. is supported by the Education Department of the Government of the Basque Country (PRE_2016_1_0057, PRE_2017_2_0224 and PRE_2018_2_0057); J.M.-G. and J.H.M. are supported by the Spanish Ministry of Education, Culture and Sport (FPU14/06837 and FPU15/02645, respectively)

Association of Breakfast Quality and Energy Density with Cardiometabolic Risk Factors in Overweight/Obese Children: Role of Physical Activity

There is a general belief that having breakfast is an important healthy lifestyle factor; however, there is scarce evidence on the influence of breakfast quality and energy density on cardiometabolic risk in children, as well as on the role of physical activity in this association. The aims of this paper were (i) to examine the associations of breakfast quality and energy density from both solids and beverages with cardiometabolic risk factors, and (ii) to explore whether physical activity levels may attenuate these relationships in children with overweight/obesity from two projects carried out in the north and south of Spain. Breakfast consumption, breakfast quality index (BQI) score, BEDs/BEDb (24 h-recalls and the KIDMED questionnaire), and physical activity (PA; accelerometry) were assessed, in 203 children aged 8–12 years who were overweight or obese. We measured body composition (Dual X-ray Absorptiometry), uric acid, blood pressure, lipid profile, gamma-glutamyl-transferase (GGT), glucose, and insulin, and calculated the HOMA and metabolic syndrome z-score. The BQI score was inversely associated with serum uric acid independently of a set of relevant confounders β = -0.172, ρ = 0.028), but the relationship was attenuated after further controlling for total PA (ρ < 0.07). BEDs was positively associated with total and HDL cholesterol, and systolic blood pressure regardless of confounders (all ρ < 0.05), while BEDb was positively associated with HOMA in either active/inactive children (all ρ < 0.03). In conclusion, higher breakfast quality and lower breakfast energy density should be promoted in overweight/obesity children to improve their cardiometabolic health.EFIGRO and ActiveBrains projects were supported by the Spanish Ministry of Industry and Competitiveness (DEP2016-78377-R and DEP2013-47540) by “Fondos Estructurales de la Unión Europea (FEDER), Una manera de hacer Europa”. The EFIGRO project was also supported by the University of the Basque Country (GIU14/21). LA was supported by a grant from the Education Department of the Government of Basque Country (PRE_2016_1_0057 and PRE_2017_2_0224), MM is supported by a grant from the Spanish Ministry of Education, Culture, and Sport (FPU14/03329) and EST17/00210, MO was supported by a grant from the Spanish Ministry of Science, Innovation, and Universities (BES-2017-080770), whereas MA was supported by a grant from the University of the Basque Country (PIF 17/186). JRR, FBO, and CC-S were also supported by grants from the Spanish Ministry of Economy and Competitiveness (RYC 2010-05957; RYC-2011-09011 and BES-2014-068829)

Combined body mass index and waist-to-height ratio and its association with lifestyle and health factors among Spanish children: the PASOS study

Background and Aims: The World Health Organization recommended simultaneous measurement of body mass index (BMI) and waist circumference (WC) and suggested joint use to predict disease risks. The aim of this study was to assess the prevalence of BMI and waist-to-height ratio (WHtR) categories among Spanish children and adolescents, as well as their associations with several lifestyle factors. Methods: Cross-sectional analysis of 8–16-year-old children and adolescents (n = 3772) were included in the PASOS nationwide representative study. Children/adolescents and their mothers/female caregivers answered a questionnaire on lifestyle and health factors. Child/adolescent anthropometrics were measured. Four combined BMI-WHtR disease risk categories were built. Results: A third of participants showed combined BMI-WHtR categories with high disease risk (12.3% ‘increased risk’, 9.7% ‘high risk’, 14.3% ‘very high risk’). Participants in the ‘very high risk’ group were less likely to be females (odds ratio 0.63; 95% CI: 0.52–0.76) and adolescents (0.60; 95% CI: 0.49–0.72), to practice ≥60 min/day of moderate-vigorous physical activity (MVPA) (0.73; 95% CI: 0.57–0.93), and to watch <120 min/day of total screen time on weekdays (0.61; 95% CI: 0.49–0.76). Mothers of participants in the ‘very high risk’ group were less likely to have a high educational level, be in the overweight or normal range, have never smoked or were former smokers, and watch <120 min/day of total screen time on weekends. Participants in the ‘increased’ and ‘high risk’ categories had mothers with normal weight and ≥60 min/day of MVPA. Participants in the ’high risk’ group did not achieve ≥60 min/day of MVPA and showed lower adherence to the mediterranean diet. Conclusions: Adherence to a healthy lifestyle in children and adolescents, but also in their mothers/female caregivers during offspring’s childhood and adolescence, is associated with low BMI-WHtR disease risk.The PASOS study was funded by Fundación PROBITAS and the Gasol Foundation. Additional funds were received from the Barça Foundation, Banco Santander, IFA, Vienna and the Fundación Deporte Joven (no references are applicable). J.A.T., C.B., M.M.G., and M.d.M.B. were funded by CIBEROBN (CB12/03/30038) of the Institute of Health Carlos III (ISCIII), and co-funded by the European Regional Development Fund

Efficacy of different 8 h time-restricted eating schedules on visceral adipose tissue and cardiometabolic health: A study protocol

Background and aims: To investigate the efficacy and feasibility of three different 8 h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) compared to each other and to a usual-care (UC) intervention on visceral adipose tissue (VAT) and cardiometabolic health in men and women. Methods and results: Anticipated 208 adults (50% women) aged 30e60 years, with overweight/ obesity (25 BMI<40 kg/m2 ) and with mild metabolic impairments will be recruited for this parallel-group, multicenter randomized controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 12 weeks: UC, early TRE, late TRE or self-selected TRE. The UC group will maintain their habitual eating window and receive, as well as the TRE groups, healthy lifestyle education for weight management. The early TRE group will start eating not later than 10:00, and the late TRE group not before 13:00. The self-selected TRE group will select an 8 h eating window before the intervention and maintain it over the intervention. The primary outcome is changes in VAT, whereas secondary outcomes include body composition and cardio metabolic risk factors. Conclusion: This study will determine whether the timing of the eating window during TRE im pacts its efficacy on VAT, body composition and cardiometabolic risk factors and provide insights about its feasibilit

Circulating miRNAs as Biomarkers of Obesity and Obesity-Associated Comorbidities in Children and Adolescents: A Systematic Review

Early detection of obesity and its associated comorbidities in children needs priority for the development of effective therapeutic intervention. Circulating miRNAs (microRNAs) have been proposed as biomarkers for obesity and its comorbidities; therefore, we conducted a systematic review to summarize results of studies that have quantified the profile of miRNAs in children and adolescents with obesity and/or associated disorders. Nine studies aiming to examine differences in miRNA expression levels between children with normal weight and obesity or between obese children with or without cardiometabolic diseases were included in this review. We identified four miRNAs overexpressed in obesity (miR-222, miR-142&ndash;3, miR-140-5p, and miR-143) and two miRNAs (miR-122 and miR-34a) overexpressed in children with obesity and nonalcoholic fatty liver disease (NAFLD) and/or insulin resistance. In conclusion, circulating miRNAs are promising diagnostic biomarkers of obesity-associated diseases such as NAFLD and type 2 diabetes already in childhood. However, more studies in children, using massive search technology and with larger sample sizes, are required to draw any firm conclusions

Peripheral blood mononuclear cells-expressed miRNA profiles derived from children with metabolic-associated fatty liver disease and insulin resistance.

miRNA have been proposed as potential biomarkers of metabolic diseases. To identify potential miRNA biomarkers of early metabolic-associated fatty liver disease (MAFLD) and/or insulin resistance (IR) in preadolescent children. A total of 70 preadolescents, aged 8.5-12 years old participated in the study. Hepatic fat was assessed by magnetic resonance imaging. Fasting blood biochemical parameters were measured and HOMA-IR calculated. Peripheral blood mononuclear cells (PBMC)-derived miRNA profiles associated with MAFLD (≥5.5% hepatic fat) and IR (HOMA-IR ≥2.5) were identified using untargeted high-throughput miRNAs sequencing (RNA-seq). A total of 2123 PBMC-derived miRNAs were identified in children with (21.4%) or without MAFLD. Among them, hsa-miR-143-3p, hsa-miR-142-5p and hsa-miR-660-5p were up-regulated, and p-hsa-miR-247, hsa-let-7a-5p and hsa-miR-6823-3p down-regulated. Importantly, children with MAFLD had consistently higher miR-660-5p expression levels than their peers without it (p  Our study results suggest circulating miR-660-5p as a potential biomarker of the presence of MAFLD in preadolescent children while circulating miR-320a, miR-142-3p, miR-190a-5p, miR-374a-5p and let-7 family miRNAs could serve as potential biomarkers of IR in children

Development of a prediction protocol for the screening of metabolic associated fatty liver disease in children with overweight or obesity.

The early detection and management of children with metabolic associated fatty liver disease (MAFLD) is challenging. To develop a non-invasive and accurate prediction protocol for the identification of MAFLD among children with overweight/obesity candidates to confirmatory diagnosis. A total of 115 children aged 8-12 years with overweight/obesity, recruited at a primary care, were enrolled in this cross-sectional study. The external validation was performed using a cohort of children with overweight/obesity (N = 46) aged 8.5-14.0 years. MAFLD (≥5.5% hepatic fat) was diagnosed by magnetic resonance imaging (MRI). Fasting blood biochemical parameters were measured, and 25 candidates' single nucleotide polymorphisms (SNPs) were determined. Variables potentially associated with the presence of MAFLD were included in a multivariate logistic regression. Children with MAFLD (36%) showed higher plasma triglycerides (TG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate transaminase (AST), glutamyl-transferase (GGT) and ferritin (p  The HEPAKID prediction protocol is an accurate, easy to implant, minimally invasive and low economic cost tool useful for the early identification and management of paediatric MAFLD in primary care