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1.
Pediatr Exerc Sci ; : 1-7, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38307007

RESUMO

PURPOSE: Associations between health-related parameters and lung function remain unclear in childhood. The study aims to evaluate the relationship between physical fitness and anthropometric parameters with the lung function of healthy scholar-aged children. METHOD: A total of 418 children aged 7 years old participated in this study. The associations of physical fitness (handgrip strength, standing broad jump, and 800-m run) and anthropometric (waist circumference and body mass index) parameters with lung function (forced vital capacity and forced expiratory volume in 1 s) were analyzed using a mixed-linear regression model. RESULTS: Girls had significantly lower forced vital capacity values (P = .006) and physical fitness (P < .030) compared to boys. On mixed-linear regression analyses, waist circumference (P = .003) was independently associated with forced vital capacity, explaining 34.6% of its variance, while handgrip strength (P = .042) and waist circumference (P = .010) were independently associated with forced expiratory volume in 1 second, accounting together for 26.5% of its variance in 7-year-old healthy children. CONCLUSIONS: Handgrip strength and waist circumference were associated with lung function in healthy children highlighting the influence of upper body muscular strength and trunk dimension on lung function. Our results corroborate the need to promote physical fitness during childhood to protect against lung complications in later on in life.

2.
Int J Mol Sci ; 25(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38256201

RESUMO

Limited nutrient supply to the fetus results in physiologic and metabolic adaptations that have unfavorable consequences in the offspring. In a swine animal model, we aimed to study the effects of gestational caloric restriction and early postnatal metformin administration on offspring's adipose tissue epigenetics and their association with morphometric and metabolic variables. Sows were either underfed (30% restriction of total food) or kept under standard diet during gestation, and piglets were randomly assigned at birth to receive metformin (n = 16 per group) or vehicle treatment (n = 16 per group) throughout lactation. DNA methylation and gene expression were assessed in the retroperitoneal adipose tissue of piglets at weaning. Results showed that gestational caloric restriction had a negative effect on the metabolic profile of the piglets, increased the expression of inflammatory markers in the adipose tissue, and changed the methylation of several genes related to metabolism. Metformin treatment resulted in positive changes in the adipocyte morphology and regulated the methylation of several genes related to atherosclerosis, insulin, and fatty acids signaling pathways. The methylation and gene expression of the differentially methylated FASN, SLC5A10, COL5A1, and PRKCZ genes in adipose tissue associated with the metabolic profile in the piglets born to underfed sows. In conclusion, our swine model showed that caloric restriction during pregnancy was associated with impaired inflammatory and DNA methylation markers in the offspring's adipose tissue that could predispose the offspring to later metabolic abnormalities. Early metformin administration could modulate the size of adipocytes and the DNA methylation changes.


Assuntos
Desnutrição , Metformina , Gravidez , Animais , Feminino , Suínos , Epigenoma , Restrição Calórica , Tecido Adiposo , Metaboloma , Metformina/farmacologia
3.
J Strength Cond Res ; 38(2): 384-393, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38088908

RESUMO

ABSTRACT: Vasileva, F, Hristovski, R, Font-Lladó, R, Georgiev, G, Sacot, A, López-Ros, V, Calleja-González, J, Barretina-Ginesta, J, López-Bermejo, A, and Prats-Puig, A. Physical exercise-induced DNA methylation in disease-related genes in healthy adults-A systematic review with bioinformatic analysis. J Strength Cond Res 38(2): 384-393, 2024-This study aimed to systematically review the existing literature regarding physical exercise (PE) and DNA methylation (DNAm) in healthy adults. Specific goals were to (a) identify differently methylated genes (DMGs) after PE intervention, their imprinting status, chromosome and genomic location, function, and related diseases; and (b) to screen for core genes and identify methylation changes of the core genes that can be modified by PE intervention. Our search identified 2,869 articles from which 8 were finally included. We identified 1851 DMGs ( p < 0.05) after PE intervention, although 45 of them were imprinted. Aerobic exercise (AE) seems to induce more DNA hypermethylation rather than hypomethylation, whereas anaerobic exercise (AN) seems to induce more DNA hypomethylation rather than hypermethylation. Aerobic exercise induced highest % of methylation changes on chromosome 6, whereas AN and mixed type (MT) on chromosome 1. Mixed type induced higher % of methylation changes close to transcription start site in comparison to AE and AN. After PE intervention, DMGs were mainly involved in fat metabolism, cell growth, and neuronal differentiation, whereas diseases regulated by those genes were mainly chronic diseases (metabolic, cardiovascular, neurodegenerative). Finally, 19 core genes were identified among DMGs, all related to protein metabolism. In conclusion, our findings may shed some light on the mechanisms explaining PE-induced health benefits such as the potential role that PE-induced DNAm may have in disease prevention and disease treatment.


Assuntos
Biologia Computacional , Metilação de DNA , Adulto , Humanos , DNA , Exercício Físico
4.
Eur J Pediatr ; 182(2): 777-784, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36478295

RESUMO

The aims of this study were as follows: (1) to assess how foot posture and morphology assessments change according to body mass index (BMI) status; (2) to determine which body composition parameter (BMI or waist circumference) correlates better with the foot posture index (FPI), arch height index (AHI), and midfoot width (MFW) in children. Foot morphometry (FPI, AHI, and MFW) and body composition (BMI and waist circumference (WC)) were assessed in a cross-sectional study of 575 children (mean age = 7.42 ± 1.67 years; 53.27% female). When comparing BMI groups, an increase of 8.3% in AHI and 13.6% in MFW (both p < 0.0001) was seen. In linear regression analyses, BMI and WC were positively associated with MFW explaining together 64.8% of its variance. Noteworthy, MFW is the most related to body composition parameters. CONCLUSION: Foot morphology assessed by FPI, AHI, and MFW differs among BMI categories in children. Noteworthy, WC correlates better with foot measures than does the more commonly used BMI, and more importantly the MFW is the foot measure best explained by children's body weight. Since foot morphometry is different among different BMI groups, children would benefit from shoes with different patterns (thinner and wider), as well as a good system to adjust midfoot height. WHAT IS KNOWN: • Children who are overweight and obese have flatter feet, when assessed using footprints. • Up to 72% of people have incorrectly fitted shoes. WHAT IS NEW: • Children with underweight have thinner and flatter feet than children with normal weight, while children with overweight and obesity have wider and higher arched feet. • Body weight is related to foot shape, which has relevance for footwear manufacturers.


Assuntos
Pé Chato , Sobrepeso , Humanos , Criança , Feminino , Pré-Escolar , Masculino , Estudos Transversais , Pé/anatomia & histologia , Antropometria , Peso Corporal , Índice de Massa Corporal , Obesidade
5.
Int J Obes (Lond) ; 46(5): 1018-1026, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35091671

RESUMO

OBJECTIVES: Maternal overfeeding during gestation may lead to adverse metabolic programming in the offspring mediated by epigenetic alterations. Potential reversal, in early life, of these alterations may help in the prevention of future cardio-metabolic conditions. In this context, our aims were: (1) to study the effects of maternal overfeeding on the metabolic and epigenetic programming of offspring's adipose tissue; and (2) to test the potential of postnatal metformin treatment to reverse these changes. METHODS: We used a swine animal model where commercial production sows were either overfed or kept under standard diet during gestation, and piglets at birth were randomly assigned to metformin (n = 16 per group) or vehicle treatment during lactation (n = 16 per group). RESULTS: Piglets born to overfed sows showed a worse metabolic profile (higher weight, weight gain from birth and abdominal circumference; all p < 0.05) together with altered serological markers (increased HOMA-IR, fructosamine, total cholesterol, C-Reactive Protein and lower HMW adiponectin; all p < 0.05). The visceral adipose tissue also showed altered morphology (increased adipocyte area, perimeter and diameter; all p < 0.05), as well as changes in gene expression (higher CCL2 and INSR, lower DLK1; all p < 0.05), and in DNA methylation (96 hypermethylated and 99 hypomethylated CpG sites; FDR < 0.05). Metformin treatment significantly ameliorated the abnormal metabolic profile, decreasing piglets' weight, weight gain from birth, abdominal circumference and fructosamine (all p < 0.05) and reduced adipocyte area, perimeter, and diameter in visceral adipose tissue (all p < 0.05). In addition, metformin treatment potentiated several associations between gene expression in visceral adipose tissue and the altered metabolic markers. CONCLUSIONS: Maternal overfeeding during gestation leads to metabolic abnormalities in the offspring, including adipose tissue alterations. Early metformin treatment mitigates these effects and could help rescue the offspring's metabolic health.


Assuntos
Metformina , Hipernutrição , Tecido Adiposo/metabolismo , Animais , Feminino , Frutosamina/metabolismo , Humanos , Metformina/farmacologia , Mães , Hipernutrição/metabolismo , Suínos , Aumento de Peso
6.
Pediatr Res ; 91(1): 107-115, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33654281

RESUMO

BACKGROUND: Accelerated catch-up growth following intrauterine restriction increases the risk of developing visceral adiposity and metabolic abnormalities. However, the underlying molecular mechanisms of such metabolic programming are still poorly understood. METHODS: A Wistar rat model of catch-up growth following intrauterine restriction was used. A gene expression array was performed in the retroperitoneal adipose tissue sampled at postnatal day (PD) 42. RESULTS: Five hundred and forty-six differentially expressed genes (DEGs) were identified (adjusted p value < 0.05). Gene ontology enrichment analysis identified pathways related to immune and lipid metabolic processes, brown fat cell differentiation, and regulation of PI3K. Ccl21, Npr3, Serpina3n, Pnpla3, Slc2a4, and Serpina12 were validated to be upregulated in catch-up pups (all p < 0.01) and related to several fat expansion and metabolic parameters, including body weight at PD42, postnatal body weight gain, white and brown adipose tissue mass, plasma triglycerides, and insulin resistance index (all p < 0.05). CONCLUSIONS: Genes related to immune and metabolic processes were upregulated in retroperitoneal adipose tissue following catch-up growth in juvenile rats and were found to be associated with fat expansion and metabolic parameters. Our results provide evidence for several dysregulated genes in white adipose tissue that could help develop novel strategies to prevent the metabolic abnormalities associated with catch-up growth. IMPACT: Catch-up growth presents several dysregulated genes in white adipose tissue related to metabolic abnormalities. Ccl21, Npr3, Serpina3n, Pnpla3, Slc2a4, and Serpina12 were validated to be upregulated in catch-up pups and related to visceral fat expansion and metabolic parameters. Profiling and validation of these dysregulated genes in visceral adipose tissue could help develop novel strategies to prevent the metabolic abnormalities associated with catch-up growth.


Assuntos
Crescimento , Gordura Intra-Abdominal/crescimento & desenvolvimento , Animais , Composição Corporal , Modelos Animais de Doenças , Feminino , Retardo do Crescimento Fetal , Regulação da Expressão Gênica , Gordura Intra-Abdominal/metabolismo , Masculino , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes
7.
Mol Cell Proteomics ; 18(9): 1745-1755, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31221719

RESUMO

Adult zebrafish, in contrast to mammals, are able to regenerate their hearts in response to injury or experimental amputation. Our understanding of the cellular and molecular bases that underlie this process, although fragmentary, has increased significantly over the last years. However, the role of the extracellular matrix (ECM) during zebrafish heart regeneration has been comparatively rarely explored. Here, we set out to characterize the ECM protein composition in adult zebrafish hearts, and whether it changed during the regenerative response. For this purpose, we first established a decellularization protocol of adult zebrafish ventricles that significantly enriched the yield of ECM proteins. We then performed proteomic analyses of decellularized control hearts and at different times of regeneration. Our results show a dynamic change in ECM protein composition, most evident at the earliest (7 days postamputation) time point analyzed. Regeneration associated with sharp increases in specific ECM proteins, and with an overall decrease in collagens and cytoskeletal proteins. We finally tested by atomic force microscopy that the changes in ECM composition translated to decreased ECM stiffness. Our cumulative results identify changes in the protein composition and mechanical properties of the zebrafish heart ECM during regeneration.


Assuntos
Matriz Extracelular/fisiologia , Coração/fisiologia , Miocárdio/citologia , Regeneração/fisiologia , Proteínas de Peixe-Zebra/análise , Animais , Fenômenos Biomecânicos , Matriz Extracelular/ultraestrutura , Proteínas da Matriz Extracelular/análise , Proteínas da Matriz Extracelular/metabolismo , Microscopia de Força Atômica , Proteômica/métodos , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
8.
Int J Obes (Lond) ; 44(1): 13-22, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31554916

RESUMO

OBJECTIVES: To study DNA methylation at the C19MC locus in the placenta and its association with (1) parental body size, (2) transmission of haplotypes for the C19MC rs55765443 SNP, and (3) offspring's body size and/or body composition at birth and in childhood. SUBJECTS AND METHODS: Seventy-two pregnant women-infant pairs and 63 fathers were included in the study. Weight and height of mothers, fathers and newborns were registered during pregnancy or at birth (n = 72). Placental DNA methylation at the C19MC imprinting control region (ICR) was quantified by bisulfite pyrosequencing. Genotyping of the SNP was performed using restriction fragment length polymorphisms. The children's body size and composition were reassessed at age 6 years (n = 32). RESULTS: Lower levels of placental C19MC methylation were associated with increased body size of mother, specifically with higher pregestational and predelivery weights and height of the mother (ß from -0.294 to -0.371; R2 from 0.04 to 0.10 and all p < 0.019), and with higher weight, height, waist and hip circumferences, and fat mass of the child (ß from -0.428 to -0.552; R2 from 0.33 to 0.56 and all p < 0.009). Parental transmission of the SNP did not correlate with an altered placental methylation status at the C19MC ICR. CONCLUSIONS: Increased maternal size is associated with reduced placental C19MC methylation, which, in turn, relate to larger body size of the child.


Assuntos
Tamanho Corporal/genética , Cromossomos Humanos Par 19/genética , Metilação de DNA/genética , MicroRNAs/genética , Placenta/metabolismo , Adulto , Criança , Cromossomos Humanos Par 19/metabolismo , Pai , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , MicroRNAs/metabolismo , Mães , Polimorfismo de Nucleotídeo Único/genética , Gravidez , Adulto Jovem
9.
Nat Mater ; 18(9): 1015-1023, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31160803

RESUMO

Epithelial repair and regeneration are driven by collective cell migration and division. Both cellular functions involve tightly controlled mechanical events, but how physical forces regulate cell division in migrating epithelia is largely unknown. Here we show that cells dividing in the migrating zebrafish epicardium exert large cell-extracellular matrix (ECM) forces during cytokinesis. These forces point towards the division axis and are exerted through focal adhesions that connect the cytokinetic ring to the underlying ECM. When subjected to high loading rates, these cytokinetic focal adhesions prevent closure of the contractile ring, leading to multi-nucleation through cytokinetic failure. By combining a clutch model with experiments on substrates of different rigidity, ECM composition and ligand density, we show that failed cytokinesis is triggered by adhesion reinforcement downstream of increased myosin density. The mechanical interaction between the cytokinetic ring and the ECM thus provides a mechanism for the regulation of cell division and polyploidy that may have implications in regeneration and cancer.


Assuntos
Divisão Celular , Citocinese , Pericárdio/citologia , Poliploidia , Peixe-Zebra , Animais , Matriz Extracelular
10.
J Strength Cond Res ; 34(11): 3078-3085, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33105357

RESUMO

Font-Lladó, R, López-Ros, V, Montalvo, AM, Sinclair, G, Prats Puig, A, and Fort-Vanmeerhaeghe, A. A pedagogical approach to integrative neuromuscular training to improve motor competence in children: a RCT. J Strength Cond Res 34(11): 3078-3085, 2020-To assess the effectiveness of a pedagogical approach to an integrative neuromuscular training (INT) program as a warm-up in physical education (PE) lessons in healthy children: (a) to improve the level of motor competence (MC) and (b) to master fundamental motor skills (FMS) patterns, considering the baseline MC level and the time spent when performing different motor tasks. One hundred ninety students (7.43 ± 0.32 years; 52% girls) were included in this randomized controlled trail and grouped up according to MC basal levels (L1-L4). Motor competence and FMS patterns (CAMSA protocol) were assessed before and after the intervention in a group-based INT warm-up (n = 97) and a group-based conventional warm-up (n = 93). The INT program improved MC (p < 0.001; d = 0.71) and FMS (p < 0.001, d = 0.52). The independent predictors of MC change were: baseline MC level (ß = -196; p < 0.012), time spent to perform the task (ß = -0.235 p < 0.003), and participation in the INT program (ß = 0.201; p < 0.005), explaining 71% of its variability. The INT warm-up shows correlations between improvements in MC in relation to time reduction (L1 p = 0.016, d, L2 p = 0.001, and L4 = 0.001) and FMS patterns (L1 p < 0.001, L2 p < 0.003, L3 p < 0.005, and L4 < 0.001) Moreover, only L3, it showed correlation between changes in time and FMS mastery (p = 0.001). Our results showed that a pedagogical approach to an INT program developed as a warm-up in primary school PE lessons can improve MC and FMS patterns in all subjects, independent of the initial MC level. More interestingly, only in L3, the improvement in MC can be explained by the balance in time required to perform the task and the level of improvement in FMS patterns.


Assuntos
Destreza Motora/fisiologia , Educação Física e Treinamento/métodos , Criança , Feminino , Humanos , Masculino , Instituições Acadêmicas , Fatores de Tempo
11.
Hum Mutat ; 40(1): 115-126, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30353964

RESUMO

In recent years, next-generation sequencing (NGS) has become a cornerstone of clinical genetics and diagnostics. Many clinical applications require high precision, especially if rare events such as somatic mutations in cancer or genetic variants causing rare diseases need to be identified. Although random sequencing errors can be modeled statistically and deep sequencing minimizes their impact, systematic errors remain a problem even at high depth of coverage. Understanding their source is crucial to increase precision of clinical NGS applications. In this work, we studied the relation between recurrent biases in allele balance (AB), systematic errors, and false positive variant calls across a large cohort of human samples analyzed by whole exome sequencing (WES). We have modeled the AB distribution for biallelic genotypes in 987 WES samples in order to identify positions recurrently deviating significantly from the expectation, a phenomenon we termed allele balance bias (ABB). Furthermore, we have developed a genotype callability score based on ABB for all positions of the human exome, which detects false positive variant calls that passed state-of-the-art filters. Finally, we demonstrate the use of ABB for detection of false associations proposed by rare variant association studies. Availability: https://github.com/Francesc-Muyas/ABB.


Assuntos
Alelos , Doença/genética , Técnicas de Genotipagem , Viés , Bases de Dados Genéticas , Estudos de Associação Genética , Genoma Humano , Genótipo , Humanos , Modelos Genéticos , Polimorfismo de Nucleotídeo Único/genética
12.
Pediatr Res ; 86(2): 195-201, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31091532

RESUMO

BACKGROUND: Although prenatal and postnatal programming of metabolic diseases in adulthood is well established, the mechanisms underpinning metabolic programming are not. Dlk1, a key regulator of fetal development, inhibits adipocyte differentiation and restricts fetal growth. METHODS: Assess DLk1 expression in a Wistar rat model of catch-up growth following intrauterine restriction. Dams fed ad libitum delivered control pups (C) and dams on a 50% calorie-restricted diet delivered pups with low birth weight (R). Restricted offspring fed a standard rat chow showed catch-up growth (R/C) but those kept on a calorie-restricted diet did not (R/R). RESULTS: Decreased Dlk1 expression was observed in adipose tissue and skeletal muscle of R/C pups along with excessive visceral fat accumulation, decreased circulating adiponectin, increased triglycerides and HOMA-IR (from p < 0.05 to p < 0.0001). Moreover, in R/C pups the reduced Dlk1 expression in adipose tissue and skeletal muscle correlated with visceral fat (r = -0.820, p < 00001) and HOMA-IR (r = -0.745, p = 0.002). CONCLUSIONS: Decreased Dlk1 expression relates to visceral fat expansion and insulin resistance in a rat model of catch-up growth following prenatal growth restriction. Modulation of Dlk1 expression could be among the targets for the early prevention of fetal programming of adult metabolic disorders.


Assuntos
Adipócitos/citologia , Retardo do Crescimento Fetal/fisiopatologia , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Gordura Intra-Abdominal/crescimento & desenvolvimento , Proteínas de Membrana/metabolismo , Animais , Diferenciação Celular , Feminino , Desenvolvimento Fetal , Insulina/metabolismo , Masculino , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Gravidez , Ratos , Ratos Wistar , Risco
14.
Int J Obes (Lond) ; 42(5): 1019-1028, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29777240

RESUMO

BACKGROUND/OBJECTIVE: Low 25-hydroxyvitamin D levels [25(OH)D] may increase the risk for cardiovascular disease (CVD). In pregnant women excessive weight gain and 25(OH)D deficiency are common complications and both could have deleterious consequences on their children. We aimed to study the relationship between serum 25(OH)D and CVD risk factors in pregnant women and in their offspring at school age. SUBJECTS/METHODS: Fasting serum 25(OH)D and its bioavailable fraction were quantified in 310 healthy pregnant women [with adequate (n = 113), insufficient (n = 113) and excessive (n = 84) weight gain]. A follow-up at 5-6 years was performed in sixty-six children born of these mothers. Lipids, insulin, glucose, and high-sensitivity C-reactive protein (hsCRP) were measured in all subjects. Children's carotid intima-media thickness (cIMT) together with visceral and intra-abdominal fat were measured by ultrasonography. RESULTS: Lower maternal 25(OH)D concentrations were associated with lower maternal age, and higher body mass index, triglycerides and hsCRP (all p < 0.05). In women with excessive weight gain during gestation, serum 25(OH)D concentrations showed independent associations with maternal hsCRP (ß = -0.283 p = 0.03) and triglycerides (ß = -0.436, p = 0.005). Maternal serum 25(OH)D concentrations were also independently associated with cIMT (ß = -0.288, p = 0.04), visceral fat (ß = -0.281, p = 0.01) and intra-abdominal fat (ß = -0.248, p = 0.01) in their children at 5-6 years. CONCLUSIONS: Lower serum 25(OH)D concentrations were related to CVD risk factors in pregnant woman and in their offspring. The cardiometabolic consequences of low 25(OH)D concentrations during pregnancy could be aggravated by excessive weight gain during gestation.


Assuntos
Doenças Cardiovasculares/epidemiologia , Ganho de Peso na Gestação/fisiologia , Gordura Intra-Abdominal/fisiologia , Vitamina D/análogos & derivados , Espessura Intima-Media Carotídea/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Gravidez , Fatores de Risco , Vitamina D/sangue
15.
Am J Obstet Gynecol ; 217(3): 350.e1-350.e13, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28502757

RESUMO

BACKGROUND: The developmentally important DLK1-DIO3 imprinted domain on human chromosome 14 is regulated by 2 differentially methylated regions, the intergenic differentially methylated region and the MEG3 differentially methylated region. OBJECTIVE: The aim was to determine the natural variation in DNA methylation at these differentially methylated regions in human placentas, and to determine its link to gene expression levels at the domain. The second goal was to explore whether the domain's methylation and gene expression correlate with prenatal and early postnatal growth of the conceptus. STUDY DESIGN: Using pyrosequencing, we determined methylation levels at CpG dinucleotides across the 2 regulatory differentially methylated regions in placentas from 91 healthy mothers. At birth, placentas and infants were weighed (gestational age 39 ± 1 weeks; birthweight SD score 0.1 ± 0.8) and placental biopsies were collected. RNA expression was quantitated by real-time polymerase chain reaction. Infants' weights and lengths were followed up monthly during the first year. RESULTS: Methylation levels at the 2 regulatory differentially methylated regions were linked and varied considerably between placentas. MEG3 promoter differentially methylated region methylation correlated negatively with weight increase (ß = -0.406, P = .001, R2 = 0.206) and length increase (ß = -0.363, P = .002, R2 = 0.230) during the first postnatal year. The methylation level of the intergenic differentially methylated region correlated with DIO3 expression (ß = 0.313, P = .032, R2 = 0.152). Furthermore, the expression of both DIO3 and RTL1 (both imprinted genes within the DLK1-DIO3 domain) was negatively associated with birthweight (ß = -0.331, P = .002, R2 = 0.165; and ß = -0.307, P = .005, R2 = 0.159, respectively). RTL1 expression, in addition, was negatively linked to birth length (ß = -0.306, P = .007, R2 = 0.162). CONCLUSION: Our combined findings strongly suggest that placental DNA methylation at the DLK1-DIO3 domain's intergenic differentially methylated region and MEG3 promoter differentially methylated region relates to measures of early human growth, and may thus contribute to its control.


Assuntos
Metilação de DNA , Desenvolvimento Fetal/genética , Recém-Nascido/crescimento & desenvolvimento , Iodeto Peroxidase/genética , Placenta/metabolismo , Proteínas da Gravidez/genética , Adulto , Peso ao Nascer/genética , Estatura/genética , Peso Corporal/genética , Epigênese Genética , Feminino , Impressão Genômica , Humanos , Masculino , Gravidez , RNA Longo não Codificante , Análise de Sequência de DNA
16.
Arterioscler Thromb Vasc Biol ; 36(1): 174-80, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26586658

RESUMO

OBJECTIVE: Body iron status has been linked to atherosclerosis in adults. The purposes of our study were to determine (1) the association between circulating ferritin levels and carotid intima-media thickness (cIMT) in a cohort of apparently healthy children and (2) the association between cIMT and parental ferritin levels. APPROACH AND RESULTS: Circulating ferritin levels (microparticle enzyme immunoassay), metabolic parameters, and cIMT (ultrasonography) were analyzed cross-sectionally in a cohort of 692 healthy white children with a mean age of 8 ± 2 years (52% girls and 48% boys). In consecutive 123 children from the cross-sectional sample, the same serum assessments were also performed at baseline in their parents, and the cIMT was repeated after 3 years of follow-up in the children at a mean age of 11 ± 2 years (53% girls and 47% boys). Weak but significant positive associations were evident between children's circulating ferritin levels and cIMT (r=0.123; P=0.001) and with the change in cIMT 3 years later a tendency was also observed (r=0.185; P=0.048). In multiple regression analyses, circulating ferritin levels contributed independently to cIMT variance (ß=0.090; P=0.026; R(2)=10%) and cIMT change variance (ß=0.216; P=0.019; R(2)= 3.4%) after controlling for body mass index, high-sensitivity C-reactive protein, age, sex, and low-density lipoprotein-cholesterol levels. This association was, however, remarkably significant (ß=0.509; P=0.001; R(2)= 20.4%) in children whose fathers had ferritin levels above the median value (122.5 ng/mL).The latter association remained significant after correction for multiple testing. Maternal's ferritin levels showed no interaction in this association. CONCLUSIONS: These results suggest a paternal-specific effect on cIMT partially reflected by father's ferritin levels.


Assuntos
Doenças das Artérias Carótidas/etiologia , Espessura Intima-Media Carotídea , Pai , Ferritinas/sangue , Adolescente , Fatores Etários , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/genética , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Regulação para Cima
17.
Clin Chem ; 62(3): 476-84, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26797688

RESUMO

BACKGROUND: CREB-regulated transcription coactivator 3 (CRTC3) is found in adipocytes, where it may promote obesity through disruption of catecholamine signaling. We wished to assess whether CRTC3 is a soluble protein secreted by adipose tissue, explore whether CRTC3 is detectable and quantifiable in the circulation, and ascertain whether CRTC3 serum concentrations are related to metabolic markers in children. METHODS: Explants of adipose tissue from 12 children were cultured to study adipocyte cell size and the secretion of CRTC3 (immunoblot and ELISA). We also performed a cross-sectional and longitudinal study in 211 asymptomatic prepubertal white children at age 7 years, 115 of whom were followed up at age approximately 10 years. We measured circulating concentrations of CRTC3 and studied associations between serum CRTC3 and metabolic markers. RESULTS: Measurable concentrations of CRTC3 were found in conditioned media of adipose tissue explants and in serum samples. CRTC3 concentrations in visceral adipose tissue were negatively associated with adipocyte cell size and positively related to adipocyte cell number (P < 0.05). In the cross-sectional study, higher CRTC3 concentrations were associated with higher body mass index (P = 0.001), waist circumference (P = 0.003), and systolic blood pressure (P = 0.007) and lower high molecular weight adiponectin (P = 0.003). In the longitudinal study, serum concentrations of CRTC3 at age approximately 7 years were associated with changes in waist circumference (ß = 0.254; P = 0.004; r = 0.145) and high molecular weight adiponectin (ß=-0.271; P = 0.014; r = 0.101), respectively, at age approximately 10 years. CONCLUSIONS: CRTC3, a newly identified protein that is related to childhood obesity, is present in the circulation, partly as a result of adipose tissue secretion. Higher serum CRTC3 concentrations are related to and predict a poorer metabolic profile in children.


Assuntos
Tecido Adiposo/metabolismo , Obesidade Infantil/fisiopatologia , Fatores de Transcrição/metabolismo , Western Blotting , Tamanho Celular , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estudos Longitudinais , Células MCF-7 , Masculino , Solubilidade
18.
Aten Primaria ; 47(7): 446-55, 2015.
Artigo em Espanhol | MEDLINE | ID: mdl-25636681

RESUMO

OBJECTIVE: Identify the level of knowledge, opinions and attitudes of medicines in general population. METHODS: Descriptive transversal study realised in a sample of≥18 years old public health users from primary health centres in the city of Barcelona. Sample has been chosen using a two phases sampling, stratified by district, gender and age. Questionnaire administered face-to-face. SPSSv15 used for the analysis. STUDY PERIOD: December 2011. RESULTS: 484 surveys has been done (IC 95%, α=5%). 53% were women and 21,3% had university studies. Medicine use: 81% had taken medicines in the last 3 months; average of 2,34. TECHNICAL CONCEPTS: 80% of medicated people know what they take and its indication. 55,6% don't know active ingredient concept. Only 35% recognise the active ingredient showed in the box of the medicine (3 cases shown) and 44,5% not one. 22,7% know the meaning of security concepts contraindication, adverse effect and drug interaction. 20% ignore. This fact grows with age and reduces with high study levels. OPINION AND ATTITUDE: Global rational use of medicines indicator obtains 5,03 from 10: 3,42 opinion and 6,51 attitude. 70% of people think there is no rational use of medicines in general and 21,3% would promote raising awareness. CONCLUSIONS: Low level of knowledge and poor attitude and opinion in rational use of medicines have been shown in this study. It is necessary involve citizens and improve their basic knowledge to promote rational use of medicines.


Assuntos
Uso de Medicamentos , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
19.
Pediatr Res ; 75(6): 793-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24603290

RESUMO

BACKGROUND: Secreted frizzled-related protein 5 (SFRP5) is an adipokine protecting against obesity-related insulin resistance and diabetes. SFRP5 binds to wingless type mouse mammary tumor virus (MMTV) integration site family member 5A (WNT5A) to improve insulin sensitivity. We performed the first study of SFRP5 and WNT5A simultaneously in children. METHODS: Prepubertal children (n = 342) were assessed for circulating SFRP5 (all subjects) and circulating WNT5A (210 subjects), and associations were sought with metabolic markers. In conditioned media of adipose tissue explants from 12 additional children, SFRP5 and WNT5A were studied further. RESULTS: The concentrations of SFRP5 and WNT5A correlated positively in serum and in conditioned media (all P < 0.001). Lower level of circulating SFRP5 (lowest quartile) was associated with higher BMI (15% increase, P < 0.0001) and lower level of high-molecular-weight adiponectin (26% decrease, P = 0.002). Circulating WNT5A related closely with insulin resistance assessed by the homeostasis model assessment for insulin resistance and hepatic markers (alanine transaminase and gamma glutamyl transpeptidase), particularly in children with lower circulating SFRP5 levels (all P < 0.004). CONCLUSION: SFRP5 and WNT5A comprise a balanced duo that may regulate metabolic homeostasis in prepubertal children.


Assuntos
Tecido Adiposo/metabolismo , Biomarcadores/metabolismo , Proteínas do Olho/sangue , Homeostase/genética , Resistência à Insulina/genética , Proteínas de Membrana/sangue , Proteínas Proto-Oncogênicas/sangue , Proteínas Wnt/sangue , Proteínas Adaptadoras de Transdução de Sinal , Adiponectina/metabolismo , Alanina Transaminase/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Espessura Intima-Media Carotídea , Criança , Proteínas do Olho/genética , Homeostase/fisiologia , Humanos , Modelos Logísticos , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas/genética , Espanha , Ultrassonografia , Proteínas Wnt/genética , Proteína Wnt-5a , gama-Glutamiltransferase/metabolismo
20.
Biofactors ; 50(1): 135-144, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37584623

RESUMO

Human milk adipokines in term babies seem partially determined by maternal factors and affect infant's development. We aimed to describe bioactive peptide concentration in very preterm human milk and associations to maternal characteristics and postnatal growth. Mothers delivering ≤32 weeks of gestation and their infant/s were recruited. At 4 weeks of lactation, an aliquot of 24-h-pooled milk was collected for exclusively breastfeeding dyads. Insulin, leptin, adiponectin, and milk fat globule epidermal growth factor-8 (MFG-E8) were measured by enzyme-linked immunoabsorbent assay in skimmed milk. One hundred mothers (28.8 ± 2.3 weeks at delivery) provided a milk sample. Milk insulin was related to gestational age, pre-pregnancy body mass index (BMI), and galactagogue treatment (final model: adjusted R2 : 0.330, p < 0.0001; adjusted ß coefficients: galactagogue treatment: 0.348, p 0.001; pre-pregnancy BMI: 0.274, p 0.009; gestational age: -0.290, p 0.007). Adiponectin was higher in mothers with gestational diabetes (30.7 ± 6.5 vs. 24.8 ± 8 ng/mL, p 0.044). Leptin was associated with pre-pregnancy BMI (Spearman's ρ: 0.648, p < 0.0001) and MFG-E8 to presence of labor and multiple pregnancy (final linear regression model, R2 : 0.073, p 0.028, adjusted ß coefficients: presence of labor -0.229, p 0.050; twins: -0.192, p 0.099). Milk adiponectin was associated with a greater decrease in length z-scores from birth to 28 days (Pearson's r: -0.225, p 0.032) and to discharge (Pearson's r: -0.290, p 0.003). Milk MFG-E8 was lower in milk of mothers whose babies experienced late-onset sepsis (13.3 ± 5.8 vs. 16.8 ± 6.3 µg/mL, p 0.023). Adipokines levels in preterm human milk are partially related to maternal metabolic status. Milk peptide concentration associates with early neonatal growth trajectories.


Assuntos
Galactagogos , Leite Humano , Recém-Nascido , Feminino , Gravidez , Humanos , Lactente , Leite Humano/metabolismo , Leptina , Adiponectina/metabolismo , Insulina/metabolismo , Adipocinas/metabolismo
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