RESUMO
BACKGROUND: Cord blood leptin and adiponectin are adipokines known to be associated with birth weight and overall infant adiposity. However, few studies have investigated their associations with abdominal adiposity in neonates. We examined maternal factors associated with cord blood leptin and adiponectin, and the association of these adipokines with neonatal adiposity and abdominal fat distribution measured by magnetic resonance imaging (MRI) in an Asian mother-offspring cohort. METHODS: Growing Up in Singapore Towards healthy Outcomes (GUSTO), is a prospective mother-offspring birth cohort study in Singapore. Cord blood plasma leptin and adiponectin concentrations were measured using Luminex and Enzyme-Linked Immunosorbent Assay respectively in 816 infants. A total of 271 neonates underwent MRI within the first 2-weeks after delivery. Abdominal superficial (sSAT), deep subcutaneous (dSAT), and intra-abdominal (IAT) adipose tissue compartment volumes were quantified from MRI images. Multivariable regression analyses were performed. RESULTS: Indian or Malay ethnicity, female sex, and gestational age were positively associated with cord blood leptin and adiponectin concentrations. Maternal gestational diabetes (GDM) positively associated with cord blood leptin concentrations but inversely associated with cord blood adiponectin concentrations. Maternal pre-pregnancy body mass index (BMI) showed a positive relationship with cord blood leptin but not with adiponectin concentrations. Each SD increase in cord blood leptin was associated with higher neonatal sSAT, dSAT and IAT; differences in SD (95% CI): 0.258 (0.142, 0.374), 0.386 (0.254, 0.517) and 0.250 (0.118, 0.383), respectively. Similarly, each SD increase in cord blood adiponectin was associated with higher neonatal sSAT and dSAT; differences in SD (95% CI): 0.185 (0.096, 0.274) and 0.173 (0.067, 0.278), respectively. The association between cord blood adiponectin and neonatal adiposity was observed in neonates of obese mothers only. CONCLUSIONS: Cord blood leptin and adiponectin concentrations were associated with ethnicity, maternal BMI and GDM, sex and gestational age. Both adipokines showed positive association with neonatal abdominal adiposity.
Assuntos
Diabetes Gestacional , Leptina , Gordura Abdominal , Adipocinas , Adiponectina , Estudos de Coortes , Feminino , Sangue Fetal , Humanos , Lactente , Recém-Nascido , Obesidade , Obesidade Abdominal , Gravidez , Estudos ProspectivosRESUMO
PURPOSE: There is altered breastmilk composition among mothers with gestational diabetes and conflicting evidence on whether breastfeeding is beneficial or detrimental to their offspring's cardiometabolic health. We aimed to investigate associations between breastfeeding and offspring's cardiometabolic health across the range of gestational glycemia. METHODS: We included 827 naturally conceived, term singletons from a prospective mother-child cohort. We measured gestational (26-28 weeks) fasting plasma glucose (FPG) and 2-h plasma glucose (2 hPG) after an oral glucose tolerance test as continuous variables. Participants were classified into 2 breastfeeding categories (high/intermediate vs. low) according to their breastfeeding duration and exclusivity. Main outcome measures included magnetic resonance imaging (MRI)-measured abdominal fat, intramyocellular lipids (IMCL), and liver fat, quantitative magnetic resonance (QMR)-measured body fat mass, blood pressure, blood lipids, and insulin resistance at 6 years old (all continuous variables). We evaluated if gestational glycemia (FPG and 2 hPG) modified the association of breastfeeding with offspring outcomes after adjusting for confounders using a multiple linear regression model that included a 'gestational glycemia × breastfeeding' interaction term. RESULTS: With increasing gestational FPG, high/intermediate (vs. low) breastfeeding was associated with lower levels of IMCL (p-interaction = 0.047), liver fat (p-interaction = 0.033), and triglycerides (p-interaction = 0.007), after adjusting for confounders. Specifically, at 2 standard deviations above the mean gestational FPG level, high/intermediate (vs. low) breastfeeding was linked to lower adjusted mean IMCL [0.39% of water signal (0.29, 0.50) vs. 0.54% of water signal (0.46, 0.62)], liver fat [0.39% by weight (0.20, 0.58) vs. 0.72% by weight (0.59, 0.85)], and triglycerides [0.62 mmol/L (0.51, 0.72) vs. 0.86 mmol/L (0.75, 0.97)]. 2 hPG did not significantly modify the association between breastfeeding and childhood cardiometabolic risk. CONCLUSION: Our findings suggest breastfeeding may confer protection against adverse fat partitioning and higher triglyceride concentration among children exposed to increased glycemia in utero.
Assuntos
Aleitamento Materno , Doenças Cardiovasculares , Diabetes Gestacional , Glicemia , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Criança , Diabetes Gestacional/patologia , Feminino , Humanos , Lipídeos , Gravidez , Estudos Prospectivos , Triglicerídeos , ÁguaRESUMO
IMPORTANCE: Screen viewing in adults has been associated with greater abdominal adiposity, with the magnitude of associations varying by sex and ethnicity, but the evidence is lacking at younger ages. We aimed to investigate sex- and ethnic-specific associations of screen-viewing time at ages 2 and 3 years with abdominal adiposity measured by magnetic resonance imaging at age 4.5 years. METHODS: The Growing Up in Singapore Towards healthy Outcomes is an ongoing prospective mother-offspring cohort study. Parents/caregivers reported the time their child spent viewing television, handheld devices, and computer screens at ages 2 and 3 years. Superficial and deep subcutaneous and visceral abdominal adipose tissue volumes were quantified from magnetic resonance images acquired at age 4.5 years. Associations between screen-viewing time and abdominal adipose tissue volumes were examined by multivariable linear regression adjusting for confounding factors. RESULTS: In the overall sample (n = 307), greater total screen-viewing time and handheld device times were associated with higher superficial and deep subcutaneous adipose tissue volumes, but not with visceral adipose tissue volumes. Interactions with child sex were found, with significant associations with superficial and deep subcutaneous and visceral adipose tissue volumes in boys, but not in girls. Among boys, the increases in mean (95% CI) superficial and deep subcutaneous and visceral adipose tissue volumes were 24.3 (9.9, 38.7), 17.6 (7.4, 27.8), and 7.8 (2.1, 13.6) mL per hour increase in daily total screen-viewing time, respectively. Ethnicity-specific analyses showed associations of total screen-viewing time with abdominal adiposity only in Malay children. Television viewing time was not associated with abdominal adiposity. CONCLUSION: Greater total screen-viewing time (and in particular, handheld device viewing time) was associated with higher abdominal adiposity in boys and Malay children. Additional studies are necessary to confirm these associations and to examine screen-viewing interventions for preventing excessive abdominal adiposity and its adverse cardiometabolic consequences.
Assuntos
Gordura Abdominal/fisiopatologia , Tempo de Tela , Experiências Adversas da Infância/psicologia , Pré-Escolar , Estudos de Coortes , Correlação de Dados , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Obesidade Infantil/epidemiologia , Fatores de Risco , Singapura/epidemiologiaRESUMO
OBJECTIVE: To identify systolic blood pressure (SBP) percentile trajectories in children and to describe the early-life risk factors and cardiometabolic correlates of those trajectories. STUDY DESIGN: Using age-, sex-, and height-specific SBP percentiles based on the American Academy of Pediatrics reference, we examined SBP trajectories using latent class mixed models from ages 3 to 8 years (n = 844) from the Growing Up in Singapore Towards healthy Outcomes-study, a Singaporean mother-offspring cohort study. We analyzed associations between SBP trajectories and early-life risk factors using multinomial logistic regression and differences across trajectories in cardiometabolic outcomes using multiple linear regression. RESULTS: Children were classified into 1 of 4 SBP percentile trajectories: "low increasing" (15%), "high stable" (47%), "high decreasing" (20%), and "low stable" (18%). Maternal hypertension during early pregnancy was a predictor of the "high stable" and "low increasing" SBP trajectories. Rapid child weight gain in the first 2 years of life was only associated with the "high stable" trajectory. Compared with children in the "low stable" trajectory, children in the "high stable" SBP trajectory had greater body mass index z scores, sum of skinfold thicknesses, waist circumference from ages 3 to 8 years, and abdominal adipose tissue (milliliters) at 4.5 years (adjusted mean difference [95% CI]: superficial and deep subcutaneous abdominal adipose tissue: 115.2 [48.1-182.3] and 85.5 [35.2-135.8]). Their fat mass (kilograms) (1.3 [0.6-2.0]), triglyceride levels (mmol/L) (0.10 [0.02-0.18]), and homeostasis model assessment of insulin resistance (0.28 [0.11 0.46]) at age 6 years were also greater but not their arterial thickness and stiffness. CONCLUSIONS: Reducing maternal blood pressure during pregnancy and infant weight gain in the first 2 years of life might help to prevent the development of high SBP.
Assuntos
Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Fatores Etários , Glicemia/metabolismo , Índice de Massa Corporal , Doenças Cardiovasculares/diagnóstico , Criança , Pré-Escolar , Colesterol/sangue , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Fatores de Risco , Singapura , Circunferência da CinturaRESUMO
BACKGROUND: Nausea and vomiting of pregnancy (NVP) is common and underlying mechanisms are poorly understood. Longer-term offspring outcomes are also not well documented. This study aimed to determine if NVP, even in milder forms, is associated with adverse pregnancy and childhood growth outcomes. METHODS: In the GUSTO prospective mother-offspring cohort, women with singleton pregnancies (n = 1172) recruited in first trimester responded to interviewer-administered questions at 26-28 weeks' gestation about earlier episodes of NVP since becoming pregnant. Pregnancy outcomes were obtained from medical records. Offspring height and weight measured at 15 time-points between birth to 72 months (m) were standardised for age and sex. RESULTS: 58.5% (n = 686) reported mild-moderate vomiting (mNVP), 10.5% (n = 123) severe vomiting (sNVP) and 5.7% (n = 67) severe vomiting with hospitalisation (shNVP). There was no difference in odds of gestational diabetes, hypertensive disorders of pregnancy, labour induction or caesarean section after adjustment for covariates. sNVP was associated with late preterm delivery [34+ 0-36+ 6 weeks', adjusted OR = 3.04 (95% CI 1.39,6.68)], without increased odds of neonatal unit admission. Compared with no NVP, boys born to mothers with sNVP were longer at birth [adjusted ß = 0.38 standard deviations (SDs) (95% CI 0.02,0.73)], remained taller [0.64 SDs (0.23,1.04) at 72 m] and heavier [0.57 SDs (0.05,1.08) at 60 m] without differences in BMI. Conversely, girls born to mothers with shNVP were lighter from 48 m [- 0.52 SDs (- 1.00, - 0.03)] onwards with lower BMI [- 0.61 SDs (- 1.12,-0.09)]. Conditional growth modelling revealed significant sex-divergence in weight-gain at birth-3 m, 6-9 m and 4-5 years. CONCLUSIONS: Severe NVP was associated with late preterm delivery, and both mild-moderate and severe NVP associated with sex-dependent differences in early childhood growth. Boys whose mothers had NVP were taller and heavier from birth with faster growth in the first year, whereas, girls had poorer weight gain and were lighter by 48 m. As even milder severities of NVP could have long-term impact on offspring growth, further research is needed to determine mechanisms involved and implications on future health. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01174875 .
Assuntos
Náusea/complicações , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Vômito/complicações , Adulto , Antropometria , Peso ao Nascer , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Náusea/epidemiologia , Gravidez , Estudos Prospectivos , Distribuição por Sexo , Singapura , Vômito/epidemiologia , Adulto JovemRESUMO
BACKGROUND/OBJECTIVES: Accumulation of lipid droplets inside skeletal muscle fibers (intramyocellular lipids or IMCL) with increasing obesity has been linked to skeletal muscle insulin resistance and risk of type 2 diabetes in both adults and prepubertal children. We aimed to evaluate the associations of race, genotype, prenatal factors, and postnatal factors with IMCL in early childhood. SUBJECTS/METHODS: This study was a secondary analysis performed on the GUSTO birth cohort. Soleus muscle IMCL of 392 children at 4.5 years of age was measured by magnetic resonance spectroscopy, of which usable imaging data were obtained from 277 children (137 Chinese, 87 Malays, and 53 Indians). Metabolic assessments (fasting glucose, insulin, and HOMA-IR) were performed at age 6. RESULTS: The mean IMCL level at 4.5 years was 0.481 ± 0.279% of water resonance (mean ± sd). Corroborating with results from adults, Indian children had the highest IMCL levels compared with Malay and Chinese children. Among the prenatal factors, the rate of gestational weight gain (GWG rate) was associated with offspring IMCL (B = 0.396 (0.069, 0.724); p = 0.018). Both race and GWG rate continued to be associated with offspring IMCL even after accounting for current offspring BMI. Postnatally, IMCL was associated with shorter breastfeeding duration (B = 0.065 (0.001, 0.128); p = 0.045) and conditional relative weight gain between ages 2 and 3 (B = 0.052 (0.012, 0.093); p = 0.012). The associations with postnatal factors were attenuated after adjusting for current offspring BMI. IMCL was positively associated with offspring BMI (B = 0.028 (0.012, 0.044); p = 0.001). IMCL levels were not associated with fasting glucose, fasting insulin, and HOMA-IR at age 6. CONCLUSION: This study provides evidence that IMCL accumulation occurs in early childhood and that developmental factors and race are associated with it. We also show that early childhood IMCL accumulation is well tolerated, suggesting that the adverse associations between IMCL and insulin resistance may emerge at older ages.
Assuntos
Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos , Músculo Esquelético , Adulto , Glicemia/análise , Índice de Massa Corporal , Pré-Escolar , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Lactente , Recém-Nascido , Resistência à Insulina , Masculino , Exposição Materna , Músculo Esquelético/química , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/metabolismo , Obesidade Infantil , Polimorfismo de Nucleotídeo Único/genética , Gravidez , Resultado da Gravidez/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The importance of ectopic fat deposition and physical fitness in the pathogenesis of insulin resistance and beta cell dysfunction in subjects from the nonobese Asians is not known. MATERIALS AND METHODS: We conducted a cross-sectional study and measured insulin sensitivity (M value; 4-hour hyperinsulinaemic-euglycaemic clamp), insulin secretion rate (3-hour mixed meal tolerance test with oral minimal modelling), percent body fat, visceral adipose tissue, intramyocellular and intrahepatic lipid contents (magnetic resonance imaging and spectroscopy), cardiorespiratory fitness (VO2 max; graded exercise test) and habitual physical activity (short International Physical Activity Questionnaire) in 60 healthy nonobese Asian subjects (BMI = 21.9 ± 1.7 kg/m2 , age = 41.8 ± 13.4 years). RESULTS: M was inversely associated with percent body fat (r = -0.460, P < 0.001), visceral fat (r = -0.623, P < 0.001) and liver fat (r = -0.601, P < 0.001), whereas insulin secretion correlated positively with these adiposity indices (percent body fat: r = 0.303, P = 0.018; visceral fat: r = 0.409, P = 0.010; hepatic fat: r = 0.393, P = 0.002). VO2 max correlated negatively with insulin secretion rate (r = -0.420, P < 0.001) and positively with M (r = 0.658, P < 0.001). The amount of vigorous physical activity was positively associated with VO2 max (r = 0.682, P < 0.001). Multiple stepwise linear regression analyses indicated that VO2 max, age, and IHTG or VAT were independent determinants of insulin sensitivity and secretion (adjusted R2 = 69% and 33%, respectively, P < 0.001). CONCLUSIONS: Increased ectopic fat deposition is associated with reduced insulin sensitivity and increased insulin secretion in healthy nonobese Asians. Poor cardiorespiratory fitness, likely due to inadequate participation in vigorous exercise, is strongly related to suboptimal metabolic function. Interventions to encourage engagement in physical activity may thus be important for improving metabolic health in nonobese Asians.
Assuntos
Glicemia/metabolismo , Gordura Intra-Abdominal/metabolismo , Aptidão Física/fisiologia , Adiposidade/fisiologia , Adulto , Idoso , Povo Asiático/etnologia , Composição Corporal , Índice de Massa Corporal , China/etnologia , Estudos Transversais , Exercício Físico/fisiologia , Feminino , Homeostase/fisiologia , Humanos , Índia/etnologia , Resistência à Insulina/fisiologia , Secreção de Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Obesidade/etnologia , Consumo de Oxigênio/fisiologia , Adulto JovemRESUMO
Type 2 diabetes in Asia occurs largely in the absence of obesity. The metabolically obese normal-weight (MONW) phenotype refers to lean subjects with metabolic dysfunction that is typically observed in people with obesity and is associated with increased risk for diabetes. Previous studies evaluated MONW subjects who had greater body mass index (BMI) or total body fat than respective control groups, making interpretation of the results difficult. We evaluated insulin sensitivity (hyperinsulinemic-euglycemic clamp); insulin secretion (mixed meal with oral minimal modeling); intra-abdominal, muscle, and liver fat contents (magnetic resonance); and fasting and postprandial glucose and insulin concentrations in 18 MONW subjects and 18 metabolically healthy controls matched for age (43 ± 3 and 40 ± 3 yr; P = 0.52), BMI (both 22 ± 1 kg/m2; P = 0.69), total body fat (17 ± 1 and 16 ± 1 kg; P = 0.33), and sex (9 men and 9 women in each group). Compared with controls, MONW subjects had an approximately twofold greater visceral adipose tissue volume and an approximately fourfold greater intrahepatic fat content (but similar muscle fat), 20-30% lower glucose disposal rates and insulin sensitivity, and 30-40% greater insulin secretion rates (all P < 0.05). The disposition index, fasting glucose, and HbA1c concentrations were not different between groups, whereas postprandial glucose and insulin concentrations were ~15% and ~65% greater, respectively, in MONW than control subjects (both P < 0.05). We conclude that the MONW phenotype is associated with accumulation of fat in the intra-abdominal area and the liver, profound insulin resistance, but also a robust ß-cell insulin secretion response that compensates for insulin resistance and helps maintain glucose homeostasis.
Assuntos
Glucose/metabolismo , Peso Corporal Ideal/fisiologia , Obesidade/metabolismo , Adulto , Composição Corporal/fisiologia , Metabolismo dos Carboidratos/fisiologia , Estudos de Casos e Controles , Feminino , Técnica Clamp de Glucose , Humanos , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Adulto JovemRESUMO
There are two types of fat tissues, white adipose tissue (WAT) and brown adipose tissue (BAT), which essentially perform opposite functions in whole body energy metabolism. There is a large interest in identifying novel biophysical properties of WAT and BAT by a quantitative and easy-to-run technique. In this work, we used high-resolution pulsed field gradient diffusion NMR spectroscopy to study the apparent diffusion coefficient (ADC) of fat molecules in rat BAT and WAT samples. The ADC of fat in BAT and WAT from rats fed with a chow diet was compared with that of rats fed with a high-fat diet to monitor how the diffusion properties change due to obesity-associated parameters such as lipid droplet size, fatty acid chain length, and saturation. Feeding a high-fat diet resulted in increased saturation, increased chain lengths, and reduced ADC of fat in WAT. The ADC of fat was lower in BAT relative to WAT in rats fed both chow and high-fat diets. Diffusion of fat was restricted in BAT due to the presence of small multilocular lipid droplets. Our findings indicate that in vivo diffusion might be a potential way for better delineation of BAT and WAT in both lean and obese states.
Assuntos
Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Obesidade/metabolismo , Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/patologia , Animais , Dieta Hiperlipídica , Metabolismo Energético , Humanos , Obesidade/diagnóstico , Obesidade/patologia , RatosRESUMO
Faster eating rates are associated with increased energy intake, but little is known about the relationship between children's eating rate, food intake and adiposity. We examined whether children who eat faster consume more energy and whether this is associated with higher weight status and adiposity. We hypothesised that eating rate mediates the relationship between child weight and ad libitum energy intake. Children (n 386) from the Growing Up in Singapore Towards Healthy Outcomes cohort participated in a video-recorded ad libitum lunch at 4·5 years to measure acute energy intake. Videos were coded for three eating-behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min). BMI and anthropometric indices of adiposity were measured. A subset of children underwent MRI scanning (n 153) to measure abdominal subcutaneous and visceral adiposity. Children above/below the median eating rate were categorised as slower and faster eaters, and compared across body composition measures. There was a strong positive relationship between eating rate and energy intake (r 0·61, P<0·001) and a positive linear relationship between eating rate and children's BMI status. Faster eaters consumed 75 % more energy content than slower eating children (Δ548 kJ (Δ131 kcal); 95 % CI 107·6, 154·4, P<0·001), and had higher whole-body (P<0·05) and subcutaneous abdominal adiposity (Δ118·3 cc; 95 % CI 24·0, 212·7, P=0·014). Mediation analysis showed that eating rate mediates the link between child weight and energy intake during a meal (b 13·59; 95 % CI 7·48, 21·83). Children who ate faster had higher energy intake, and this was associated with increased BMI z-score and adiposity.
Assuntos
Adiposidade , Comportamento Infantil , Fenômenos Fisiológicos da Nutrição Infantil , Dieta/efeitos adversos , Ingestão de Energia , Comportamento Alimentar , Sobrepeso/etiologia , Adiposidade/etnologia , Índice de Massa Corporal , Comportamento Infantil/etnologia , Desenvolvimento Infantil , Fenômenos Fisiológicos da Nutrição Infantil/etnologia , Pré-Escolar , Estudos de Coortes , Dieta/etnologia , Ingestão de Energia/etnologia , Comportamento Alimentar/etnologia , Feminino , Humanos , Almoço , Masculino , Inquéritos Nutricionais , Sobrepeso/etnologia , Obesidade Infantil/etnologia , Obesidade Infantil/etiologia , Singapura , Fatores de Tempo , Gravação em VídeoRESUMO
BACKGROUND: The influence of prenatal exposure to per- and poly- fluoroalkyl substances (PFAS) on birth size and offspring adiposity is unclear, especially for the newer, shorter-chained replacement PFAS. METHODS: In the GUSTO multi-ethnic Singaporean mother-offspring cohort, 12 PFAS were measured in 783 cord plasma samples using ultra-performance-liquid chromatography-tandem-mass-spectrometer (UPLC-MS/MS). Outcomes included offspring anthropometry, other indicators of body composition/metabolic health, and MRI-derived abdominal adiposity (subset) at birth and 6 years of age. PFAS were modeled individually, in categories of long-chain and short-chain PFAS, and as scores of three principal components (PC) derived using PC analysis (PC1, PC2, and PC3 reflect predominant exposure patterns to "very-long-PFAS", "long-PFAS", and "short-PFAS", respectively). Associations with outcomes were assessed using multivariable linear regressions, adjusted for important covariates such as maternal sociodemographic and lifestyle factors. RESULTS: Overall, cord PFAS levels showed either no or positive associations (mostly for long-chain PFAS) with birth weight, length and head circumference. In general, PFAS were associated with higher neonatal abdominal adiposity, driven by shorter-chain PFAS. Perfluoroheptanoic acid (PFHpA) was associated with higher volumes of superficial subcutaneous adipose tissue (sSAT) (3.75 [1.13, 6.37] mL per SD increase in PFAS) and internal adipose tissue (IAT) (1.39 [0.41, 2.38] mL). Higher levels of perfluorobutanesulfonic acid (PFBS), short-chain PFAS, and PC3 were associated with higher IAT volume (ß range 1.22-1.41 mL/SD, all P < 0.02), especially in girls. Higher PC3 score was additionally associated with higher sSAT (3.12 [0.45, 5.80] mL) volume. At age 6 years, most observed associations did not persist. No consistent associations were observed between PFAS and whole-body adiposity measures. CONCLUSIONS: Fetal exposure to emerging short-chain PFAS was associated with higher abdominal adiposity at birth but not at age 6 years. Further research is needed to replicate the findings and to determine if these effects may reappear beyond early childhood. Population exposure to newer PFAS and consequent health impact must be monitored.
Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Efeitos Tardios da Exposição Pré-Natal , Recém-Nascido , Gravidez , Criança , Feminino , Humanos , Pré-Escolar , Adiposidade , Cromatografia Líquida , Estudos Prospectivos , Espectrometria de Massas em Tandem , Obesidade , Composição Corporal , Obesidade AbdominalRESUMO
BACKGROUND: Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD. OBJECTIVES: To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD. METHODS: In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed. RESULTS: In the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss. CONCLUSION: Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome. TRIAL REGISTRATION NUMBER: This trial was registered at the clinicaltrials.gov as NCT05259475.
Assuntos
Dieta Mediterrânea , Ácidos Graxos , Hepatopatia Gordurosa não Alcoólica , Feminino , Humanos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fígado/metabolismo , Redução de Peso , Ácidos Graxos Insaturados , ColesterolRESUMO
BACKGROUND: The timing of introduction of complementary foods and the duration of breastfeeding (BF) have been independently associated with child overweight and obesity; however, their combined influence on body fat partitioning and cardiometabolic risk is unclear. OBJECTIVE: We investigated the associations of the timing of introduction of complementary foods, the duration of BF, and their interaction with child adiposity and cardiometabolic risk markers. METHODS: We analyzed data from 839 children in the prospective Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Mothers reported the age at which infants were first fed complementary foods and BF duration, classified as early (≤4 mo) versus typical (>4 mo) complementary feeding (CF) and short (≤4 mo) versus long (>4 mo) duration of any BF, respectively. We measured adiposity and cardiometabolic risk markers at the age of 6 y and examined their associations with infant feeding patterns using multiple regression, adjusting for sociodemographics, parents' body mass index (BMI), maternal factors, birth weight for gestational age, and infant weight gain. RESULTS: Of 839 children, 18% experienced early CF, whereas 54% experienced short BF. Short (vs. long) BF and early (vs. typical) CF were independently associated with higher z-scores of BMI [ß (95% confidence interval), short BF, 0.18 standard deviation score (SDS) (-0.01, 0.38); early CF, 0.34 SDS (0.11, 0.57)] and sum of skinfolds [short BF, 1.83 mm (0.05, 3.61); early CF, 2.73 mm (0.55, 4.91)]. Children who experienced both early CF and short BF (vs. typical CF-long BF) had synergistically higher diastolic blood pressure [1.41 mmHg (-0.15, 2.97), P-interaction = 0.023] and metabolic syndrome score [0.81 (0.16, 1.47), P-interaction = 0.081]. Early CF-long BF (vs. early CF-short BF) was associated with a lower systolic blood pressure [-3.74 mmHg (-7.01, -0.48)], diastolic blood pressure [-2.29 mmHg (-4.47, -0.11)], and metabolic syndrome score [-0.90 (-1.80, 0.00)]. CONCLUSIONS: A combination of early CF and short BF was associated with elevated child adiposity and cardiometabolic markers. Longer BF duration may protect against cardiometabolic risk associated with early CF. This trial was registered at clinicaltrials.gov as NCT01174875.
Assuntos
Doenças Cardiovasculares , Síndrome Metabólica , Criança , Feminino , Humanos , Lactente , Índice de Massa Corporal , Aleitamento Materno , Doenças Cardiovasculares/prevenção & controle , Estudos de Coortes , Obesidade , Estudos ProspectivosRESUMO
BACKGROUND: Existing literature has highlighted structural, physiological, and pathological disparities among abdominal adipose tissue (AAT) sub-depots. Accurate separation and quantification of these sub-depots are crucial for advancing our understanding of obesity and its comorbidities. However, the absence of clear boundaries between the sub-depots in medical imaging data has challenged their separation, particularly for internal adipose tissue (IAT) sub-depots. To date, the quantification of AAT sub-depots remains challenging, marked by a time-consuming, costly, and complex process. PURPOSE: To implement and evaluate a convolutional neural network to enable granular assessment of AAT by compartmentalization of subcutaneous adipose tissue (SAT) into superficial subcutaneous (SSAT) and deep subcutaneous (DSAT) adipose tissue, and IAT into intraperitoneal (IPAT), retroperitoneal (RPAT), and paraspinal (PSAT) adipose tissue. MATERIAL AND METHODS: MRI datasets were retrospectively collected from Singapore Preconception Study for Long-Term Maternal and Child Outcomes (S-PRESTO: 389 women aged 31.4 ± 3.9 years) and Singapore Adult Metabolism Study (SAMS: 50 men aged 28.7 ± 5.7 years). For all datasets, ground truth segmentation masks were created through manual segmentation. A Res-Net based 3D-UNet was trained and evaluated via 5-fold cross-validation on S-PRESTO data (N = 300). The model's final performance was assessed on a hold-out (N = 89) and an external test set (N = 50, SAMS). RESULTS: The proposed method enabled reliable segmentation of individual AAT sub-depots in 3D MRI volumes with high mean Dice similarity scores of 98.3%, 97.2%, 96.5%, 96.3%, and 95.9% for SSAT, DSAT, IPAT, RPAT, and PSAT respectively. CONCLUSION: Convolutional neural networks can accurately sub-divide abdominal SAT into SSAT and DSAT, and abdominal IAT into IPAT, RPAT, and PSAT with high accuracy. The presented method has the potential to significantly contribute to advancements in the field of obesity imaging and precision medicine.
Assuntos
Gordura Abdominal , Obesidade , Adulto , Masculino , Criança , Humanos , Feminino , Estudos Retrospectivos , Gordura Abdominal/diagnóstico por imagem , Gordura Subcutânea Abdominal , Redes Neurais de Computação , Tecido Adiposo , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Longitudinal assessment of the determinants of obesogenic growth trajectories in childhood can suggest appropriate developmental windows for intervention. METHODS: Latent class growth mixture modelling was used to identify body mass index (BMI) z-score trajectories from birth to age 6 years in 994 children from a prospective mother-offspring cohort (Chinese, Indian and Malay ethnicities) based in Singapore. We evaluated the early-life determinants of the trajectories as well as their associations with cardiometabolic risk markers at age 6 years. RESULTS: Five BMI z-score trajectory patterns were identified, three within the healthy weight range, alongside early-acceleration and late-acceleration obesogenic trajectories. The early-acceleration pattern was characterized by elevated fetal abdominal circumference growth velocity, BMI acceleration immediately after birth and crossing of the obesity threshold by age 2 years. The late-acceleration pattern had normal fetal growth and BMI acceleration after infancy, and approached the obesity threshold by age 6 years. Abdominal fat, liver fat, insulin resistance and odds of pre-hypertension/hypertension were elevated in both groups. Indian ethnicity, high pre-pregnancy BMI, high polygenic risk scores for obesity and shorter breastfeeding duration were common risk factors for both groups. Malay ethnicity and low maternal educational attainment were uniquely associated with early BMI acceleration, whereas nulliparity and obesogenic eating behaviours in early childhood were uniquely associated with late BMI acceleration. CONCLUSION: BMI acceleration starting immediately after birth or after infancy were both linked to early cardiometabolic alterations. The determinants of these trajectories may be useful for developing early risk stratification and intervention approaches to counteract metabolic adversities linked to childhood obesity.
Assuntos
Doenças Cardiovasculares , Obesidade Infantil , Feminino , Criança , Pré-Escolar , Humanos , Gravidez , Obesidade Infantil/epidemiologia , Estudos Prospectivos , Índice de Massa Corporal , Fatores de RiscoRESUMO
Both hyperthyroidism and elevated plasma branched chain amino acids (BCAA) are associated with insulin resistance. BCAA utilization and clearance relative to thyroid status changes remains unclear. We investigate amino acids changes, specifically BCAA, during the transition from hyperthyroidism to euthyroidism, and the impact of active brown adipose tissue (BAT) on the metabolic effects of BCAA. Newly diagnosed Graves' disease participants were recruited. Hyperthyroidism was treated via a titration dosing regimen of thionamide anti-thyroid drug to establish euthyroidism over 12-24 weeks. All underwent energy expenditure (EE) measurement within a chamber calorimeter, 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging and plasma amino acids measurement during hyperthyroidism and euthyroidism. PET BAT maximum standardized uptake value (SUVmax), SUVmean and MR supraclavicular fat fraction (FF) quantified BAT activity. Twenty-two patients completed the study. Plasma BCAA level was significantly reduced in BAT-positive but not in BAT-negative patients during the transition from hyperthyroidism to euthyroidism. Plasma valine but not leucine and isoleucine correlated positively with insulin and HOMA-IR in hyperthyroidism. Plasma valine, leucine and isoleucine correlated with insulin and HOMA-IR in euthyroidism. Plasma valine correlated with insulin and HOMA-IR in BAT-negative but not in BAT-positive participants in both hyperthyroid and euthyroid state. However, the change (i.e. decrease) in plasma valine concentration from hyperthyroid to euthyroid state was affected by BAT-status. BAT utilizes and promotes BCAA plasma clearance from hyperthyroid to euthyroid state. Active BAT can potentially reduce circulating BCAA and may help to ameliorate insulin resistance and improve metabolic health.Clinical trial registration: The trial was registered at clinicaltrials.gov as NCT03064542.
Assuntos
Hipertireoidismo , Resistência à Insulina , Tecido Adiposo Marrom/metabolismo , Aminoácidos de Cadeia Ramificada/metabolismo , Fluordesoxiglucose F18/metabolismo , Humanos , Hipertireoidismo/metabolismo , Insulina/metabolismo , Isoleucina/metabolismo , Leucina/metabolismo , Valina/metabolismoRESUMO
CONTEXT: The kynurenine pathway generates metabolites integral to energy metabolism, neurotransmission, and immune function. Circulating kynurenine metabolites positively correlate with adiposity in children and adults, yet it is not known whether this relationship is present already at birth. OBJECTIVE: In this prospective longitudinal study, we investigate the relationship between cord blood kynurenine metabolites and measures of adiposity from birth to 4.5 years. METHODS: Liquid chromatography-tandem mass spectrometry was used to quantify cord blood kynurenine metabolites in 812 neonates from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. Fat percentage was measured by air displacement plethysmography and abdominal adipose tissue compartment volumes; superficial (sSAT) and deep subcutaneous (dSAT) and internal adipose tissue were quantified by magnetic resonance imaging at early infancy in a smaller subset of neonates, and again at 4 to 4.5 years of age. RESULTS: Cord blood kynurenine metabolites appeared to be higher in female newborns, higher in Indian newborns compared with Chinese newborns, and higher in infants born by cesarean section compared with vaginal delivery. Kynurenine, xanthurenic acid, and quinolinic acid were positively associated with birthweight, but not with subsequent weight during infancy and childhood. Quinolinic acid was positively associated with sSAT at birth. Kynurenic acid and quinolinic acid were positively associated with fat percentage at 4 years. CONCLUSION: Several cord blood kynurenine metabolite concentrations were positively associated with birthweight, with higher kynurenic acid and quinolinic acid correlating to higher percentage body fat in childhood, suggesting these cord blood metabolites as biomarkers of early childhood adiposity.
Assuntos
Cinurenina , Obesidade Infantil , Adiposidade , Adulto , Peso ao Nascer , Cesárea , Criança , Pré-Escolar , Feminino , Sangue Fetal/metabolismo , Humanos , Lactente , Recém-Nascido , Ácido Cinurênico/metabolismo , Estudos Longitudinais , Obesidade Infantil/metabolismo , Gravidez , Estudos Prospectivos , Ácido Quinolínico/metabolismoRESUMO
Brown adipose tissue (BAT) is a promising weapon to combat obesity and metabolic disease. BAT is thermogenic and consumes substantial amounts of glucose and fatty acids as fuel for thermogenesis and energy expenditure. To study BAT function in large human longitudinal cohorts, safe and precise detection methodologies are needed. Although regarded a gold standard, the foray of PET-CT into BAT research and clinical applications is limited by its high ionizing radiation doses. Here, we show that brown adipocytes release exosomes in blood plasma that can be utilized to assess BAT activity. In the present study, we investigated circulating protein biomarkers that can accurately and reliably reflect BAT activation triggered by cold exposure, capsinoids ingestion and thyroid hormone excess in humans. We discovered an exosomal protein, methylene tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L), to be overexpressed and detectable in plasma for all three modes of BAT activation in human subjects. This mitochondrial protein is packaged as a cargo within multivesicular bodies of the endosomal compartment and secreted as exosomes via exocytosis from activated brown adipocytes into the circulation. To support MTHFD1L as a conserved BAT activation response in other vertebrates, we examined a rodent model and also proved its presence in blood of rats following BAT activation by cold exposure. Plasma concentration of exosomal MTHFD1L correlated with human BAT activity as confirmed by PET-MR in humans and supported by data from rats. Thus, we deduce that MTHFD1L appears to be overexpressed in activated BAT compared to BAT in the basal nonstimulated state.
Assuntos
Tecido Adiposo Marrom , Exossomos , Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Metabolismo Energético , Exossomos/metabolismo , Humanos , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , NADP/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Ratos , Tetra-Hidrofolato Desidrogenase/metabolismoRESUMO
BACKGROUND: Early epidemiological studies have associated low birthweight with increased cardiovascular risk. We aimed to examine whether the fat and fat-free components of birthweight have differing relationships with childhood cardiovascular risk markers. METHODS: In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, air displacement plethysmography was conducted within 24 h after delivery in 290 naturally conceived singletons. We investigated associations of newborn cohort-specific standardized z-score of fat mass, fat-free mass, body fat percentage and birthweight on child (at 6 years of age) carotid intima-media thickness, pulse wave velocity, blood pressure, prehypertension/hypertension (>110/70 mmHg) and standardized systolic and diastolic blood pressure (SBP and DBP) trajectories (at 3-6 years of age), taking account of maternal education, height, tobacco exposure, parity, ethnicity, child's sex, gestational age, age at follow-up, and other maternal factors. RESULTS: Clear inverse associations were seen for blood pressure with z-score of fat mass [SBP, ß (95% CI): -1.31 mmHg (-2.57, -0.06); DBP: -0.79 mmHg (-1.74, 0.15)] and body fat percentage [SBP: -1.46 mmHg (-2.73, -0.19); DBP: -0.80 mmHg (-1.75, 0.16)], but not with fat-free mass [SBP: 0.27 mmHg (-1.29, 1.83)]; DBP: -0.14 mmHg (-1.30, 1.03)]. Being in the lowest tertile of fat mass or body fat percentage was associated with higher blood pressure trajectories and prehypertension/hypertension risk [OR (95% CI), fat mass: 4.23 (1.41, 12.68); body fat percentage: 3.22 (1.09, 9.53)] without concomitantly higher overweight/obesity risk. CONCLUSIONS: At birth, low adiposity was associated with increased childhood blood pressure. Low newborn adiposity might serve as a marker of poor fetal growth or suboptimal intrauterine conditions associated with hypertension risk later in life.
Assuntos
Doenças Cardiovasculares , Hipertensão , Pré-Hipertensão , Recém-Nascido , Gravidez , Feminino , Criança , Humanos , Pré-Escolar , Peso ao Nascer , Doenças Cardiovasculares/epidemiologia , Estudos Prospectivos , Espessura Intima-Media Carotídea , Estudos de Coortes , Análise de Onda de Pulso , Fatores de Risco , Pressão Sanguínea , Composição Corporal , Hipertensão/epidemiologia , Obesidade , Fatores de Risco de Doenças Cardíacas , Índice de Massa CorporalRESUMO
OBJECTIVE: To evaluate the relationship of the levels of maternal alcohol consumption during the 1 year before pregnancy recognition with childhood cardiorenal, metabolic, and neurocognitive health. METHODS: In 1106 women and their children from the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort, quantity of maternal alcohol consumption in the 12 months prior to pregnancy recognition was categorized as high (≥75th percentile: 1.9âg/day), low (<1.9âg/day), and none, and frequency of alcohol consumption was categorized as high (≥2-3 times/week), low (<2-3 times/week), and none. Offspring MRI-based abdominal fat depot, kidney, and brain volumes, blood pressure, metabolic syndrome score, and cognitive intelligence scores were assessed. Child prehypertension/hypertension at age 6 years was defined using a simplified pediatric threshold of 110/70âmmHg. RESULTS: The average maternal alcohol consumption in the year prior to pregnancy recognition was 2.5âg/day, which is lower than the daily maximal limit of one standard drink (10âg) recommended for women by Singapore's Ministry of Health. After adjusting for participant characteristics, alcohol consumption at least 1.9âg/day was associated with over two-fold higher risk (risk ratioâ=â2.18, Pâ=â0.013) of child prehypertension and 15% greater kidney growth between early infancy and age 6 years (Pâ=â0.040) compared with abstinence. Alcohol consumption was not associated with metabolic and neurocognitive health at age 6-7 years. The associations with high frequency of alcohol consumption were concordant with those obtained for quantity of alcohol consumption. CONCLUSION: Maternal self-reported alcohol consumption at least 1.9âg/day prior to pregnancy recognition was associated with increased risk of child prehypertension and rapid kidney growth. Our findings highlight the potential detrimental effects of low periconceptional alcohol consumption, below national guidelines on offspring cardiorenal health.