Maternal metabolic health drives mesenchymal stem cell metabolism and infant fat mass at birth.
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ABSTRACT:
SUBMITTER: Erickson ML
PROVIDER: S-EPMC8410068 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Maternal obesity is a global health problem that increases offspring obesity risk. The metabolic pathways underlying early developmental programming in human infants at risk for obesity remain poorly understood, largely due to barriers in fetal/infant tissue sampling. Utilizing umbilical cord-derived mesenchymal stem cells (uMSC) from offspring of normal weight and obese mothers, we tested whether energy metabolism and gene expression differ in differentiating uMSC myocytes and adipocytes, in relation to maternal obesity exposures and/or neonatal adiposity. Biomarkers of incomplete ?-oxidation were uniquely positively correlated with infant adiposity and maternal lipid levels in uMSC myocytes from offspring of obese mothers only. Metabolic and biosynthetic processes were enriched in differential gene expression analysis related to maternal obesity. In uMSC adipocytes, maternal obesity and lipids were associated with downregulation in multiple insulin-dependent energy-sensing pathways including PI3K and AMPK. Maternal lipids correlated with uMSC adipocyte upregulation of the mitochondrial respiratory chain but downregulation of mitochondrial biogenesis. Overall, our data revealed cell-specific alterations in metabolism and gene expression that correlated with maternal obesity and adiposity of their offspring, suggesting tissue-specific metabolic and regulatory changes in these newborn cells. We provide important insight into potential developmental programming mechanisms of increased obesity risk in offspring of obese mothers.
| S-EPMC5752288 | biostudies-literature
Project description:ObjectiveIn human studies, new model systems are needed for improved mechanistic investigation of developmental predisposition for metabolic disease but also to serve as benchmarks in early life prevention or intervention efforts. In this regard, human infant umbilical cord-derived mesenchymal stem cells (MSCs) are an emerging tool. However, long-term clinical relevance to in vivo markers of metabolic disease is unknown.MethodsIn a cohort of 124 mother/child dyads, this study tested the hypothesis that triglyceride content (TG) of infant MSCs undergoing adipogenesis in vitro (MSC-TG) is associated with in vivo adiposity (percent fat mass) from birth to early childhood and with fasting glucose and insulin in early childhood.ResultsMSC-TG was positively associated with in vivo child adiposity at birth, age 4 to 6 months, and age 4 to 6 years. MSC-TG was associated with fasting glucose, but not insulin, at 4 to 6 years. Importantly, MSC-TG explained an additional 13% variance in child adiposity at 4 to 6 years, after accounting for other established birth predictors (weight and percent fat mass at birth) and other established covariates related to child adiposity (e.g., breastfeeding exposure, physical activity).ConclusionsThis work demonstrates the strength of the MSC model for predicting offspring metabolic phenotype into childhood, even when considering the important contribution of other early life risk factors.
| S-EPMC9782692 | biostudies-literature
Project description:BackgroundMaternal adaptations may vary by foetal sex. Whether male infants influence long-term mortality in mothers remains uncertain.ObjectiveThe objective of the study was to examine whether male infants increase the risk of maternal mortality.MethodsThis study included pregnant women enrolled at 12 US sites from 1959 to 1966 in the Collaborative Perinatal Project (CPP). Collaborative Perinatal Project records were linked to the National Death Index and the Social Security Master Death File to ascertain deaths until 2016. Foetal sex was determined by infant sex at birth, defined as the total number of male or female infants in pregnancies prior to or during enrolment in the CPP. In secondary analyses, exposure was defined as infant sex at the last CPP delivery. Outcomes included all-cause and underlying causes of mortality. We used Cox proportional hazards models weighted by the number of prior live births and stratified our models by parity and race/ethnicity.ResultsAmong 48,188 women, 50.8% had a male infant at their last registered CPP pregnancy and 39.0% had a recorded death after a mean follow-up of 47.8 years (SD 10.5 years). No linear association was found between the number of liveborn males and all-cause mortality (primipara women: HR 1.02, 95% CI 0.95, 1.09, multipara women, 1 prior live birth: HR 0.96, 95% CI 0.89, 1.03, multipara women, ≥2 prior live births: HR 0.97, 95% CI 0.85, 1.11). A similar trend was noted for cardiovascular- and cancer-related mortality. At the last delivery, women with a male infant did not have an increased risk of all-cause or cause-specific mortality compared to women with a female infant. These findings were consistent across racial/ethnic groups.ConclusionsWomen who give birth to male infants, regardless of number, are not at increased risk of all-cause and cause-specific mortality. These findings suggest that giving birth to male infants may not independently influence the long-term health of women.
| S-EPMC10448630 | biostudies-literature
Project description:Maternal vitamin D status has been associated with both gestational diabetes mellitus (GDM) and fetal growth restriction, however, the evidence is inconsistent. In Finland, maternal vitamin D status has improved considerably due to national health policies. Our objective was to compare maternal 25-hydroxy vitamin D concentrations [25(OH)D] between mothers with and without GDM, and to investigate if an association existed between maternal vitamin D concentration and infant birth size.This cross-sectional study included 723 mother-child pairs. Mothers were of Caucasian origin, and infants were born at term with normal birth weight. GDM diagnosis and birth size were obtained from medical records. Maternal 25(OH)D was determined on average at 11 weeks of gestation in pregnancy and in umbilical cord blood (UCB) at birth.GDM was observed in 81 of the 723 women (11%). Of the study population, 97% were vitamin D sufficient [25(OH)D???50 nmol/L]. There was no difference in pregnancy 25(OH)D concentration between GDM and non-GDM mothers (82 vs 82 nmol/L, P?=?0.99). Regression analysis confirmed no association between oral glucose tolerance test results and maternal 25(OH)D (P?>?0.53). Regarding the birth size, mothers with optimal pregnancy 25(OH)D (? 80 nmol/L) had heavier newborns than those with suboptimal pregnancy 25(OH)D (P?=?0.010). However, mothers with optimal UCB 25(OH)D had newborns with smaller head circumference than those with suboptimal 25(OH)D (P?=?0.003), which was further confirmed as a linear association (P?=?0.024).Maternal vitamin D concentration was similar in mothers with and without GDM in a mostly vitamin D sufficient population. Associations between maternal vitamin D status and birth size were inconsistent. A sufficient maternal vitamin D status, specified as 25(OH)D above 50 nmol/L, may be a threshold above which the physiological requirements of pregnancy are achieved.The project protocol is registered in ClinicalTrials.gov in November 8, 2012 ( NCT01723852 ).
| S-EPMC5732505 | biostudies-literature
Project description:Childhood obesity can be predicted by metabolic signaling at birth. Understanding what exposure factors, such as prenatal mental health, predict metabolic signaling at birth are important for understanding the etiology of childhood metabolic dysregulation. Drawing on data from the Born in Bradford (BiB) multi-ethnic birth cohort in the United Kingdom (N = 2962 dyads), this study examined associations between maternal prenatal mental health symptoms and infant leptin and adiponectin. We tested whether total maternal prenatal symptoms as well as specific symptom subscales forecasted infant cord blood levels of leptin and adiponectin. We found that higher total maternal mental health symptoms and somatic symptoms, specifically, predicted lower infant cord blood leptin. We did not find evidence that maternal prenatal mental health symptoms predicted adiponectin. Together, our findings suggest that maternal mental health symptoms may become biologically embedded through infant metabolic changes via leptin.
| S-EPMC8474689 | biostudies-literature
Project description:The biophysical factors of biomaterials such as their stiffness regulate stem cell differentiation. Energy metabolism has been revealed an essential role in stem cell lineage commitment. However, whether and how extracellular matrix (ECM) stiffness regulates energy metabolism to determine stem cell differentiation is less known. Here, the study reveals that stiff ECM promotes glycolysis, oxidative phosphorylation, and enhances antioxidant defense system during osteogenic differentiation in MSCs. Stiff ECM increases mitochondrial fusion by enhancing mitofusin 1 and 2 expression and inhibiting the dynamin-related protein 1 activity, which contributes to osteogenesis. Yes-associated protein (YAP) impacts glycolysis, glutamine metabolism, mitochondrial dynamics, and mitochondrial biosynthesis to regulate stiffness-mediated osteogenic differentiation. Furthermore, glycolysis in turn regulates YAP activity through the cytoskeletal tension-mediated deformation of nuclei. Overall, our findings suggest that YAP is an important mechanotransducer to integrate ECM mechanical cues and energy metabolic signaling to affect the fate of MSCs. This offers valuable guidance to improve the scaffold design for bone tissue engineering constructs.
| S-EPMC10909577 | biostudies-literature
Project description:ContextIt is unclear how fat mass accretion in early life is related to glucose-insulin homeostasis.ObjectiveExamine associations of fat and fat-free mass accretion from birth to early childhood with glucose-insulin homeostasis in early childhood in a multi-ethnic cohort.MethodsObservational Healthy Start study with data collection from 2010 to 2020. Air displacement plethysmography at birth and 4.8 (SD 0.7) years estimated fat mass percent (FMP, %), fat mass index (FMI, kg/m2), and fat-free mass index (FFMI, kg/m2). General population recruited from academic obstetrics clinics in Denver, Colorado, consisting of 419 mother/offspring dyads. The main outcome measures were fasting glucose, insulin, homeostasis model assessment-2 insulin resistance (HOMA2-IR), and beta-cell function (HOMA2-B) at 4.8 years.ResultsGreater fat mass accretion from birth to early childhood was associated with higher fasting glucose (ΔFMP β = 0.20 [95% CI 0.06-0.34], ΔFMI β = 0.90 [0.30-1.50]) in participants of Hispanic, Black, and Other races/ethnicities, while greater fat-free mass accretion was associated with higher fasting glucose in non-Hispanic White participants (ΔFFMI β = 0.76 [0.21-1.32]). Overall, greater fat, but not fat-free, mass accretion was also associated with higher insulin (ΔFMP β = 0.14 [0.09-0.18], ΔFMI 0.71 [0.51-0.92]), HOMA2-IR (FMP β = 0.02 [0.01-0.02], ΔFMI β = 0.09 [0.06-0.12]), and HOMA2-B (ΔFMP β = 0.92 [0.18-1.36], ΔFMI β = 4.76 [2.79-6.73]).ConclusionGreater fat mass accretion in infancy and childhood is associated with shifts in fasting glucose in children of Hispanic, Black, and Other races/ethnicities at 5 years of age. Body composition beginning in early life is relevant for metabolic health, and precise assessments of adiposity in pediatric research are needed.
| S-EPMC8118576 | biostudies-literature
Project description:Artificial sweetener consumption by pregnant women has been associated with an increased risk of infant obesity, but the underlying mechanisms are unknown. We aimed to determine if maternal consumption of artificially sweetened beverages (ASB) during pregnancy is associated with modifications of infant gut bacterial community composition and function during the first year of life, and whether these alterations are linked with infant body mass index (BMI) at one year of age. We studied 100 infants from the prospective Canadian CHILD Cohort Study, selected based on maternal ASB consumption during pregnancy (50 non-consumers and 50 daily consumers). BMI was higher among ASB-exposed infants. Infant stool (16S rRNA gene sequencing) and urine (untargeted metabolomics) were acquired in early (3-4 months) and late (12 months) infancy. We identified four microbiome clusters, of which two recapitulated the maturation trajectory of the infant gut bacterial communities from immature (Cluster 1) to mature (Cluster 4) and two deviated from this trajectory (Clusters 2 and 3). Maternal ASB consumption did not differ between clusters, but was associated with community-level shifts in infant gut bacterial taxonomy structure and depletion of several Bacteroides sp. in Cluster 2. In the complete dataset, urine succinate and spermidine levels at 3 months were higher in ASB-exposed infants, and urine succinate was positively associated with BMI at one-year-old. Overall, gestational exposure to ASB was associated with gut microbiota structure in infants from Cluster 2, and gut microbiota structure was associated with infant BMI. Gestational exposure to ASB was positively associated with infant urine succinate and spermidine. Succinate was found to mediate 29% of the effect of ASB exposure on BMI at one-year-old, revealing a potential role of this metabolite in increased infant weight linked to gestational ASB consumption. As we face an unprecedented rise in childhood obesity, future studies should evaluate the causal relationships between maternal ASB consumption (a modifiable exposure), gut microbiota and metabolites, infant metabolism, and body composition.
| S-EPMC7781635 | biostudies-literature
Project description:Obesity and depression are two common medical problems that pregnant women present with in antenatal care. Overweight and obesity at the beginning of the pregnancy, and excessive weight gain during pregnancy, are independent explanatory variables for fetal birthweight and independent risk factors for giving birth to a large for gestational age (LGA) infant. However, the effect of co-morbid depression has received little attention. This study set out to investigate if maternal body mass index (BMI) in early pregnancy moderates antenatal depression effects on infant birthweight. 3965 pregnant women participated in this longitudinal cohort study, where cases (n = 178) had Edinburgh Postnatal Depression Scale (EPDS) score ≥ 17 in gestational week 17 or 32, and remaining women (n = 3787) were used as controls. The influence of maternal BMI and antenatal depressive symptoms on standardized birthweight was evaluated by analysis of covariance, with adjustment for relevant confounders. Depressed women with BMI 25.0 kg/m2 or more gave birth to infants with significantly greater standardized birthweight than non-depressed overweight women, whereas the opposite pattern was noted in normal weight women (BMI by antenatal depressive symptoms interaction; F(1,3839) = 6.32; p = 0.012. The increased birthweight in women with co-prevalent overweight and depressive symptoms was not explained by increased weight gain during the pregnancy. Maternal BMI at the beginning of pregnancy seems to influence the association between antenatal depressive symptoms and infant birthweight, but in opposite directions depending on whether the pregnant women is normal weight or overweight. Further studies are needed to confirm our finding.
| S-EPMC6470129 | biostudies-other
Project description:Background: Infant body mass index (BMI) peak has received much interest recently as a potential predictor of future obesity and metabolic risk. No studies, however, have examined infant BMI peak in Asian populations, in whom the risk of metabolic disease is higher.Methods: We utilized data among 1020 infants from a mother-offspring cohort, who were Singapore citizens or permanent residents of Chinese, Malay or Indian ethnicity with homogeneous parental ethnic backgrounds, and did not receive chemotherapy, psychotropic drugs or have diabetes mellitus. Ethnicity was self-reported at recruitment and later confirmed using genotype analysis. Subject-specific BMI curves were fitted to infant BMI data using natural cubic splines with random coefficients to account for repeated measures in each child. We estimated characteristics of the child's BMI peak [age and magnitude at peak, average pre-peak velocity (aPPV)]. Systolic (SBP) and diastolic blood pressure (DBP), BMI, sum of skinfolds (SSF) and fat-mass index (FMI) were measured during a follow-up visit at age 48 months. Weighted multivariable linear regression was used to assess the predictors (maternal BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational age and breastfeeding duration) of infant BMI peak and its associations with outcomes at 48 months. Comparisons between ethnicities were tested using Bonferroni post-hoc correction.Results: Of 1020 infants, 80.5% were followed up at the 48-month visit. Mean (SD) BMI, SSF and FMI at 48 months were 15.6 (1.8) kg/m 2 , 16.5 (5.3) mm and 3.8 (1.3) kg/m 2 , respectively. Mean (SD) age at peak BMI was 6.0 (1.6) months, with a magnitude of 17.2 (1.4) kg/m 2 and pre-peak velocity of 0.7 (0.3) kg/m 2 /month. Compared with Chinese infants, the peak occurred later in Malay {B [95% confidence interval (CI): 0.64 mo (0.36, 0.92)]} and Indian infants [1.11 mo (0.76, 1.46)] and was lower in magnitude in Indian infants [-0.45 kg/m 2 (-0.69, -0.20)]. Adjusting for maternal education, BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational-age and breastfeeding duration, higher peak and aPPV were associated with greater BMI, SSF and FMI at 48 months. Age at peak was positively associated with BMI at 48 months [0.15 units (0.09, 0.22)], whereas peak magnitude was associated with SBP [0.17 units (0.05, 0.30)] and DBP at 48 months [0.10 units (0.01, 0.22)]. Older age and higher magnitude at peak were associated with increased risk of overweight at 48 months [Relative Risk (95% CI): 1.35 (1.12-1.62) for age; 1.89 (1.60-2.24) for magnitude]. The associations of BMI peak with BMI and SSF at 48 months were stronger in Malay and Indian children than in Chinese children.Conclusions: Ethnic-specific differences in BMI peak characteristics, and associations of BMI peak with early childhood cardio-metabolic markers, suggest an important impact of early BMI development on later metabolic outcomes in Asian populations.
| S-EPMC5231275 | biostudies-literature