Offspring Adiposity Research Articles

Prenatal maternal vitamin D deficiency sex-dependently programs adipose tissue metabolism and energy homeostasis in offspring.

In utero environment is crucial to ensure normal development of the fetus and to program metabolic health throughout the life. Beside macronutrients, the role of micronutrients, including vitamin D, begins to be explore. The aim of this study was to decipher the impact of maternal vitamin D deficiency (VDD), in normal and high-fat (HF) diet context, on adipose tissue metabolism and energy homeostasis in offspring, considering sex-specific responses. Body weight, energy expenditure, and spontaneous activity was differential impacted in juvenile male and female offspring born from VDD mice. In adulthood, a HF diet combined with maternal VDD disrupted glucose homeostasis and adiposity in male offspring but not in females. Such phenotypes were associated to different transcriptomic profiles in adipose tissue, which could be related to differential modulation of plasma 17β-estradiol concentrations. Thus, maternal VDD sex-dependently modulated metabolic fate of the offspring, especially when associated with HF diet in adulthood.

Association between maternal smoking during pregnancy and offspring overweight in U.S.-born children.

The criticism of the literature on smoking during pregnancy and offspring overweight was the confounding from postnatal factors. Interaction between gestational age and prenatal maternal smoking has not yet assessed. We used the Third National Health and Nutrition Examination Survey (1988-1994), linked with natality files of US-born singletons aged 2 to 6 years. A body mass index in the 85th percentile or higher were considered overweight, including obesity. Gestational age was dichotomized as preterm (<37 weeks, n = 240) or full-term (n = 2125). Smoking status during pregnancy was ascertained by a questionnaire-based interview during National Health and Nutrition Examination Survey. The prevalence of offspring overweight and obesity combined was 17.3% (SE = 1.3%). And 24.0% (1.3%) of mothers smoked while pregnant. A significant interaction was observed between maternal smoking and gestational age. In preterm children, a higher prevalence of overweight (34.3% [6.7%]) was found among the offspring of smoking mothers compared to non-smoking mothers (15.8% [3.6%]). After adjustment for socio-demographics, prenatal and postnatal factors, in preterm born offspring, the odds ratio of being born to smoking mothers was 2.46 (95% confidence intervals: 1.13-5.37) among children with overweight/obesity compared to children with healthy weight born to non-smoking mothers. In full-term children, the OR of being born to smoking mothers was 0.72 (0.50-1.03) among offspring with overweight/obesity relative to offspring with healthy weight born to non-smoking mothers. Maternal smoking during pregnancy was strongly associated with offspring overweight and obesity in preterm births after control for postnatal factors. Preterm children of smoking mothers should be prioritized for obesity prevention.

Determinants of insulin resistance in children exposed to gestational diabetes in utero.

The evolution of increased adiposity and cardiometabolic risk in offspring exposed to maternal gestational diabetes (GDM) is not well understood. (a) To evaluate the impact of in utero exposure to GDM and maternal weight status on homeostasis model assessment of insulin resistance (HOMA-IR) in the offspring longitudinally from 1 to 3 years of age and (b) to compare body mass index (BMI) and HOMA-IR in GDM and non-GDM exposed offspring at 1 and 3 years of age. A prospective cohort of children born to mothers with and without GDM underwent metabolic characterization between birth and 3 years of age. In the overall cohort, weight gain between birth and 3 years of age was positively associated with HOMA-IR (β = 0.1491, P = .02), independent of maternal weight status. HOMA-IR was not different between GDM and non-GDM exposed children from 1 to 3 years of age; however, BMI z score was greater in GDM exposed children at 3 years of age. Among non-GDM exposed children, male sex predicted a 35.1% lower HOMA-IR (P = .03). In GDM exposed offspring, a 1 unit increase in maternal insulin sensitivity predicted a 20.8% decrease in HOMA-IR (P = .002). Overall, weight gain in the first 3 years of life was positively associated with HOMA-IR, while insulin sensitivity of mothers with GDM negatively predicted HOMA-IR in the offspring. Our findings indicate the need to target weight trajectories in early life, as well as maternal factors during gestation to improve metabolic outcomes in the offspring, particularly those exposed to GDM.

Mild maternal sleep-disordered breathing during pregnancy and offspring growth and adiposity in the first 3 years of life

Sleep-disordered breathing (SDB) during pregnancy has been linked to adverse fetal outcomes. Since the intrauterine milieu plays a critical role in childhood growth, we explored the interactions between maternal SDB and offspring growth and adiposity patterns during infancy. Fifty-eight healthy women with uncomplicated pregnancies underwent an objective sleep study and laboratory evaluation during the third trimester, their offspring underwent a 3-year growth surveillance. The 14 (24.1%) women with SDB had a higher body mass index (BMI) (P = 0.003), elevated C-reactive protein levels (P = 0.003), and decreased HDL-cholesterol levels (P = 0.009) than the women without SDB. A general linear model evaluated the interactions between maternal SDB and offspring growth and adiposity measurements after controlling for gestational age and maternal and paternal BMIs. The offspring of mothers with SDB had a significantly smaller head circumference at birth (P = 0.004), with a distinctive pattern of catchup growth by the end of the first year of life (P = 0.018). Their growth pattern was distinguished by compromised birth weight-to-length, rapid catch-up growth, and an increase in both weight-to-length and triceps thickness by the age of three (P < 0.001 and P = 0.001, respectively). Our findings suggest that maternal SDB during pregnancy affects head circumference growth and adiposity acquisition from birth through infancy.

Neonatal administration of kaempferol does not alter satiety but increases somatic growth and reduces adiposity in offspring of high-fat diet dams

AimThe aim of this study was to evaluate the effects of maternal exposure to a high-fat diet associated with neonatal administration of kaempferol on somatic growth, biochemical profile and feeding behavior in offspring. Materials and methodsWistar rats were distributed according to diet during pregnancy and lactation into Control (C; 3.4 kcal/g; 12% kcal/lipids) or High-fat (HFD; 4.6 kcal/g; 51% kcal/lipids) groups. In the offspring, vehicle (V) or kaempferol (K, 1 mg/kg) were administered from the 8th until the 21st postnatal day (PND). Maternal body weight (BW), caloric intake and adiposity were measured. In the offspring, somatic growth parameters were evaluated on the 7th, 14th, 21st, 25th and 30th PND, except for BW, which was measured from the 8th to the 21st and from the 25th to the 30th PND. Feeding behavior was assessed by food intake and behavioral satiety sequence (BSS) on the 30th PND. The biochemical profile and relative weight of adipose tissue of offspring were also measured. Key findingsDams exposed to HFD showed no difference in body weight and caloric intake but exhibited increased adiposity. Neonatal administration of kaempferol increased body weight after weaning and somatic growth in the offspring of HFD dams. Neonatal kaempferol also reduced adiposity and serum creatinine levels in offspring. Neither maternal diet nor kaempferol altered offspring feeding behavior. SignificanceNeonatal administration of kaempferol promotes increased somatic growth post-weaning, reduces adiposity, and does not alter feeding behavior in offspring from high-fat dams.

Impact of Overweight in Mens with Family History of Hypertension: Early Heart Rate Variability and Oxidative Stress Disarrangements.

Aim To evaluate cardiovascular, autonomic, and oxidative stress markers in eutrophic and overweight offspring of hypertensive parents comparing them to eutrophic and overweight offspring of normotensive parents. Methods We conducted a cross-sectional study. We selected 71 male and sedentary subjects, divided into 4 groups: eutrophic group with a negative family history of hypertension (EH-, n = 18) or positive family history of hypertension (EH+, n = 17), overweight group with a negative family history of hypertension (OH-, n = 19) or a positive family history of hypertension (OH+, n = 17), and aged between 18 and 35 years. Results Blood glucose was higher in the OH+ group when compared to other groups. Diastolic blood pressure was increased in OH- and OH+ groups when compared to eutrophic groups. Regarding the HRV, the LF abs was higher in OH- and OH+ groups when compared to the EH- group. LF/HF values were higher in EH+ and OH+ groups when compared to the EH- and OH- groups. As to oxidative stress and the metabolism of nitric oxide, we observed an increase in hydrogen peroxide and nitrite levels in the OH+ group, and in the NADPH oxidase in OH- and OH+ groups when compared to the other groups. Conclusion Our findings demonstrate that the overweight group with a family history of hypertension presented all the dysfunctions observed in isolation from these risk factors. We observed an exacerbation of cardiac sympathetic modulation and early prooxidants increase, which may be associated with target organ damage and cardiovascular risk in this population.

Maternal high-fat diet stimulates proinflammatory pathway and increases the expression of Tryptophan Hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF) in adolescent mice hippocampus

Maternal high-fat diet (HFD) consumption can promote a systemic inflammatory condition that may impair the offspring brain development, damaging memory and learning, when it reaches the hippocampus. This study aims to evaluate maternal HFD effects, during pregnancy and lactation, upon dams/mice offspring nutritional status, protein and gene expression of inflammatory pathway (JNK, pJNK and TNF-α), serotonin system molecules (Tryptophan Hydroxylase 2 (TPH2), key-enzyme of serotonin synthesis, serotonin transporter (SERT); 5-HT1A serotonergic receptor (5-HT1A)) and brain derived neurotrophic factor (BDNF) on recently weaned mice offspring hippocampus. Female Swiss mice were fed a control diet (CD, 11,5% fat) or a HFD (45.0% fat) from pre-mating to lactation. After weaning, the offspring received CD up to 28 post-natal days (PND28). Body weight and visceral adiposity (retroperitoneal and gonadal adipose tissue) of dams and offspring were measured. After euthanasia, the offspring hippocampus was dissected for evaluations of BDNF, inflammatory pathway and serotonergic system molecules protein and gene expression, through the techniques of Western Blotting, RTqPCR and ELISA. Our findings show that, during pregnancy, HFD-dams and HFD-offspring exhibited an increase in body weight gain and visceral adipose tissue compared to control animals. The hippocampus of HFD-offspring showed increased protein expression of TPH2, BDNF, pJNK and increased mRNA levels of TNF-α. However, the TPH2 increase in HFD-offspring did not alter hippocampal serotonin levels quantified through ELISA. Maternal HFD promoted an obesity phenotype in its offspring with increased body weight and visceral adiposity, increased protein and gene expression of the pro-inflammatory proteins pJNK and TNF-α. These changes were accompanied by increased TPH2 and BDNF protein expression. Thus, our findings show that maternal HFD during gestation and lactation increased pJNK and TNF-α expression in their offspring hippocampus indicating a pro-inflammatory state, with increased BDNF expression and alterations in its serotonergic system reflected by increased TPH2 expression.

Maternal weight change between successive pregnancies: an opportunity for lifecourse obesity prevention.

Maternal obesity is a major risk factor for adverse health outcomes for both the mother and the child, including the serious public health problem of childhood obesity which is globally on the rise. Given the relatively intensive contact with health/care professionals following birth, the interpregnancy period provides a golden opportunity to focus on preconception and family health, and to introduce interventions that support mothers to achieve or maintain a healthy weight in preparation for their next pregnancy. In this review, we summarise the evidence on the association between interpregnancy weight gain with birth and obesity outcomes in the offspring. Gaining weight between pregnancies is associated with an increased risk of large-for-gestational age (LGA) birth, a predictor of childhood obesity, and weight loss between pregnancies in women with overweight or obesity seems protective against recurrent LGA. Interpregnancy weight loss seems to be negatively associated with birthweight. There is some suggestion that interpregnancy weight change may be associated with preterm birth, but the mechanisms are unclear and the direction depends if it is spontaneous or indicated. There is limited evidence on the direct positive link between maternal interpregnancy weight gain with gestational diabetes, pre-eclampsia, gestational hypertension and obesity or overweight in childhood, with no studies using adult offspring adiposity outcomes. Improving preconception health and optimising weight before pregnancy could contribute to tackling the rise in childhood obesity. Research testing the feasibility, acceptability and effectiveness of interventions to optimise maternal weight and health during this period is needed, particularly in high-risk and disadvantaged groups.

Systematic review: Symptoms of parental depression and anxiety and offspring overweight.

ABSTRACTOBJECTIVE To evaluate the existing literature on the association between parents’ depression and anxiety and their influence on their children’s weight during childhood, identifying possible mechanisms involved in this association.METHODS A systematic search of the literature was conducted in the PubMed, PsycINFO and SciELO databases, using the following descriptors: (maternal OR mother* OR parent* OR paternal OR father) AND (“common mental disorder” OR “mental health” OR “mental disorder” OR “depressive disorder” OR depress* OR anxiety OR “anxiety disorder”) AND (child* OR pediatric OR offspring) AND (overweight OR obes* OR “body mass index” OR BMI). A total of 1,187 articles were found after peer selection.RESULTS In total, 16 articles that met the inclusion criteria were selected for the review. Most of them investigated depressive symptoms and only three, symptoms of maternal anxiety. The evaluated studies suggested a positive association between symptoms of maternal depression and higher risk of childhood obesity. The results diverged according to the chronicity of depressive symptoms (episodic or recurrent depression) and income of the investigated country (high or middle income). Mechanisms were identified passing by quality of parenthood, affecting behaviors related to physical activity and child-feeding, as mediators of the association.CONCLUSIONS We conclude there is evidence of a positive relationship between the occurrence of maternal symptoms of depression and anxiety and childhood obesity. It is emphasized the need for a better understanding on the effect of depressive symptoms and the contextual factors involved in this relationship so that effective intervention strategies can be implemented.

Maternal body mass index and risks of neonatal mortality and offspring overweight and obesity: Findings from 0.5 million samples in 61 low- and middle-income countries.

Evidence on associations of maternal overweight and obesity with risks of offspring mortality and obesity is limited in low- and middle-income countries (LMICs). We aimed to assess the associations of maternal overweight and obesity with neonatal mortality, and offspring overweight and obesity in LMICs. Data were from the Demographic and Health Surveys in 61 LMICs. A total of 507 203 pairs of mother and offspring were included in the analysis for neonatal mortality, and 455 534 pairs in the analysis for overweight and obesity in offspring aged 3 to 59 months. Survey logistic regression models were used to examine the associations of maternal overweight and obesity with neonatal mortality, and offspring overweight and obesity in consideration of complex survey design with adjustment for potential covariates. Compared with mothers having normal weight, neonatal mortality risks were increased in mothers having overweight, modest obesity and severe obesity, with ORs (95% CIs) of 1.32 (1.17-1.49), 1.50 (1.27-1.77) and 1.56 (1.22-1.98), respectively. In addition, offspring with mothers having overweight, modest obesity and severe obesity were at increased risks of overweight (with ORs [95% CIs] of 1.32 [1.24-1.40], 1.61 [1.48-1.74] and 1.69 [1.52-1.88], respectively) and obesity (with ORs [95% CIs] of 1.23 [1.13-1.34], 1.22 [1.10-1.35] and 1.42 [1.21-1.66], respectively). Our results suggest that maternal overweight and obesity increased the risks of neonatal mortality, and offspring overweight and obesity in LMICs. Maternal weight control should be considered as the highest priority goal for preventing offspring's adverse health outcomes in LMICs.

1245-P: Maternal HbA1c Is Related to Childhood Fat Mass and Only Partially Mediated by Neonatal Fat Mass

Maternal diabetes during pregnancy impacts offspring body composition and has been associated with greater offspring adiposity across the life course. However, the extent to which the relationship between maternal glycemia and offspring adiposity during later life is independent of neonatal adiposity is unclear. In a prospective study of 544 mother-child pairs in the Healthy Start Study, we estimated the total effect of maternal HbA1c on childhood fat mass (FM) %, and the direct effect independent of neonatal FM %. We measured maternal fasting HbA1c at a gestational age of 20-34 weeks, and offspring FM % using air displacement plethysmography at birth and during childhood (age 4-7 y). We used multivariable linear regression with HbA1c tertiles (T1 [reference], T2, T3) as the exposure, neonatal FM % as the mediator, and childhood FM % as the outcome. A counterfactual-based approach was used to estimate total and direct effects, while also accounting for exposure-mediator interaction. Covariates were maternal race, education, gestational weight gain and smoking, and offspring sex and age. The medians (interquartile ranges) of the HbA1c tertiles were T1: 4.80 (3.70, 4.90), T2: 5.05 (5.00, 5.10), and T3: 5.30 (5.20, 6.30). The estimated total effect on child FM % was 1.27 (95% CI: 0.00, 2.54) units higher for T2 vs. T1, and 1.53 (0.23, 2.82) units higher for T3 vs. T1 (P-trend=0.02). After adjusting for pre-pregnancy BMI, the total effect was 1.18 (-0.09, 2.44) and 1.31 (0.00, 2.62) units higher for T2 vs. T1 and T3 vs. T1, respectively (P-trend=0.04). The direct effect after accounting for neonatal FM % was slightly attenuated (T2 vs. T1: 1.14 [-0.11, 2.39], T3 vs. T1: 1.20 [-0.11, 2.51]; P-trend=0.07). Excluding women with gestational diabetes mellitus (n=27) did not substantially impact the results. Our data suggest that maternal glycemia during pregnancy, even within normal levels, may influence childhood adiposity through pathways that are in part mediated by programming of neonatal adiposity. Disclosure E.C. Francis: None. B. Ringham: None. D.H. Glueck: None. W. Perng: None. D. Dabelea: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (5R01DK076648-10)

Change in modifiable maternal characteristics and behaviours between consecutive pregnancies and offspring adiposity: A systematic review.

SummaryCausal evidence links modifiable maternal exposures during the periconceptional period with offspring obesity. The interconception period may be an important time to intervene. We systematically identified studies examining change in modifiable maternal exposures between pregnancies and offspring adiposity. We searched for longitudinal studies published between 1990 and 2019, which included measurements taken on at least two occasions in the period from 1 year prior to the conception of the first birth to the time of the second birth, and which included a measure of adiposity in second, or higher order, siblings. Age, ethnicity and genetics were not considered modifiable; all other factors including length of the interpregnancy interval were. Eleven studies satisfied the inclusion criteria. Higher interpregnancy weight gain or loss, maternal smoking inception, mothers smoking in their first pregnancy and quitting, increasing the number of cigarettes smoked and longer interpregnancy intervals were positively associated with adiposity in second or higher order children. Vaginal birth after caesarean delivery was protective. Further research is needed to ascertain whether the risk of adiposity is fixed based on first pregnancy exposures or if interpregnancy change alters the risk for a subsequent child. This can inform the type and effectiveness of interventions for mothers prior to a subsequent pregnancy.

A Prospective Study of Relations Among Infant, Maternal, and Paternal Adiposity Indicators

Abstract Objectives This study examines relations of infant birth size and growth with maternal early pregnancy BMI, gestational weight gain (GWG), postpartum weight change and paternal body size. Methods Infant birth size (small for gestational age- SGA, &amp;lt;10th percentile and large for gestational age- LGA, &amp;gt;90th percentile) and weight-for-length z-scores (WFLz) were calculated from anthropometrics obtained at birth (n = 331), 6 weeks, 6 months and 12 months of age. Maternal early pregnancy BMI, GWG, % of GWG lost (%GWGL), and return to early pregnancy weight (EPW) were derived from height and weight measured from early pregnancy (mean ± SD = 9.9 ± 1.7 weeks gestation) through 12 months postpartum. Mothers reported father's baseline body size via Stunkard figure ratings. Logistic regressions and linear mixed models estimated relations of SGA, LGA and WFLz with parent weight indicators. Multiplicative interaction terms tested interactions of maternal BMI with pregnancy and postpartum weight change, and of paternal with maternal weight indicators. Analyses controlled for maternal height, demographics, child sex, gestational age at delivery, and delivery mode. Results LGA was positively associated with maternal BMI (OR = 1.10, 95%CI:1.05–1.16, P &amp;lt; 0.001) but not GWG. SGA was associated with lower odds of excessive GWG (OR = 0.24, 95%CI:0.07–0.79, P = 0.02) but was not associated with maternal BMI. Paternal body size was not associated with LGA or SGA. WFLz was positively associated with maternal BMI (β ± SE = 0.03 ± 0.09 P = 0.001), but not GWG, %GWGL, EPW, or paternal body size. However, WFLz was positively associated with GWG in mothers with low (&amp;lt;25) but not high (≥25) early pregnancy BMI (β ± SE interaction term = −0.004 ± 0.002, P = 0.04). Paternal body size did not modify associations of maternal with infant weight indicators. Conclusions Maternal BMI was consistently associated with birth size and infant adiposity development, and associations were not modified by paternal body size. Whether pre-pregnancy interventions are more effective than pregnancy interventions for reducing offspring overweight in women with high BMI is an important area of future investigation. Funding Sources This research was supported by the NICHD Intramural Research Program.

High placental inositol content associated with suppressed pro-adipogenic effects of maternal glycaemia in offspring: the GUSTO cohort

Background/ObjectivesMaternal glycaemia promotes fetal adiposity. Inositol, an insulin sensitizer, has been trialled for gestational diabetes prevention. The placenta has been implicated in how maternal hyperglycaemia generates fetal pathophysiology, but no studies have examined whether placental inositol biology is altered with maternal hyperglycaemia, nor whether such alterations impact fetal physiology. We aimed to investigate whether the effects of maternal glycaemia on offspring birthweight and adiposity at birth differed across placental inositol levels.MethodsUsing longitudinal data from the Growing Up in Singapore Towards healthy Outcomes cohort, maternal fasting glucose (FPG) and 2-hour plasma glucose (2hPG) were obtained in pregnant women by a 75-g oral glucose tolerance test around 26 weeks’ gestation. Relative placental inositol was quantified by liquid chromatography-mass spectrometry. Primary outcomes were birthweight (n = 884) and abdominal adipose tissue (AAT) volumes measured by neonatal MRI scanning in a subset (n = 262) of term singleton pregnancies. Multiple linear regression analyses were performed.ResultsPlacental inositol was lower in those with higher 2hPG, no exposure to tobacco smoke antenatally, with vaginal delivery and shorter gestation. Positive associations of FPG with birthweight (adjusted β [95% CI] 164.8 g [109.1, 220.5]) and AAT (17.3 ml [11.9, 22.6] per mmol glucose) were observed, with significant interactions between inositol tertiles and FPG in relation to these outcomes (p < 0.05). Stratification by inositol tertiles showed that each mmol/L increase in FPG was associated with increased birthweight and AAT volume among cases within the lowest (birthweight = 174.2 g [81.2, 267.2], AAT = 21.0 ml [13.1, 28.8]) and middle inositol tertiles (birthweight = 202.0 g [103.8, 300.1], AAT = 19.7 ml [9.7, 29.7]). However, no significant association was found among cases within the highest tertile (birthweight = 81.0 g [−21.2, 183.2], AAT = 0.8 ml [−8.4, 10.0]).ConclusionsHigh placental inositol may protect the fetus from the pro-adipogenic effects of maternal glycaemia. Studies are warranted to investigate whether prenatal inositol supplementation can increase placental inositol and reduce fetal adiposity.

Nonnutritive sweetener consumption during pregnancy, adiposity, and adipocyte differentiation in offspring: evidence from humans, mice, and cells

Obesity often originates in early life, and is linked to excess sugar intake. Nonnutritive sweeteners (NNS) are widely consumed as "healthier" alternatives to sugar, yet recent evidence suggests NNS may adversely influence weight gain and metabolic health. The impact of NNS during critical periods of early development has rarely been studied. We investigated the effect of prenatal NNS exposure on postnatal adiposity and adipocyte development. In the CHILD birth cohort (N = 2298), we assessed maternal NNS beverage intake during pregnancy and child body composition at 3 years, controlling for maternal BMI and other potential confounders. To investigate causal mechanisms, we fed NNS to pregnant C57BL6J mice at doses relevant to human consumption (42 mg/kg/day aspartame or 6.3 mg/kg/day sucralose), and assessed offspring until 12 weeks of age for: body weight, adiposity, adipose tissue morphology and gene expression, glucose and insulin tolerance. We also studied the effect of sucralose on lipid accumulation and gene expression in cultured 3T3-L1 pre-adipocyte cells. In the CHILD cohort, children born to mothers who regularly consumed NNS beverages had elevated body mass index (mean z-score difference +0.23, 95% CI 0.05-0.42 for daily vs. no consumption, adjusted for maternal BMI). In mice, maternal NNS caused elevated body weight, adiposity, and insulin resistance in offspring, especially in males (e.g., 47% and 15% increase in body fat for aspartame and sucralose vs. controls, p < 0.001). In cultured adipocytes, sucralose exposure at early stages of differentiation caused increased lipid accumulation and expression of adipocyte differentiation genes (e.g., C/EBP-α, FABP4, and FASN). These genes were also upregulated in adipose tissue of male mouse offspring born to sucralose-fed dams. By triangulating evidence from humans, mice, and cultured adipocytes, this study provides new evidence that maternal NNS consumption during pregnancy may program obesity risk in offspring through effects on adiposity and adipocyte differentiation.

Gestational Diabetes Mellitus Is Associated with Age-Specific Alterations in Markers of Adiposity in Offspring: A Narrative Review.

Maternal hyperglycemia alters an offspring’s metabolic health outcomes, as demonstrated by the increased risk for obesity, impaired glucose handling and diabetes from early childhood onwards. Infant growth patterns are associated with childhood adiposity and metabolic health outcomes and, as such, can be used as potential markers to detect suboptimal metabolic development at an early age. Hence, we aimed to assess whether gestational diabetes mellitus (GDM) has an impact on offspring growth trajectories. Outcomes included weight gain (WG), body mass index (BMI), and skin fold thickness (SFT) measured at least at two time points from birth to later childhood. In addition, we explored the role of early life pre- and post-natal nutritional modifiable factors on longitudinal growth in infants of mother with GDM (GDM–F1). Despite the large heterogeneity of the studies, we can still conclude that GDM seems to be associated with altered growth outcomes in the offspring. More specifically, these alterations in growth outcomes seem to be rather time-specific. Increased SFT were reported particularly at birth, with limited information on reporting SFT between 2–5 y, and increased adiposity, measured via SFT and BMI, appeared mainly in later childhood (5–10 y). Studies evaluating longitudinal growth outcomes suggested a potential role of early life nutritional modifiable factors including maternal nutrition and breastfeeding. These may impact the cycle of adverse metabolic health by attenuating growth outcome alterations among GDM–F1. Conclusions: Timely diagnoses of growth deviations in infancy are crucial for early identification of GDM–F1 who are at risk for childhood overweight and metabolic disease development.

Maternal Obesity and Western-Style Diet Impair Fetal and Juvenile Offspring Skeletal Muscle Insulin-Stimulated Glucose Transport in Nonhuman Primates.

Infants born to mothers with obesity have a greater risk for childhood obesity and metabolic diseases; however, the underlying biological mechanisms remain poorly understood. We used a Japanese macaque model to investigate whether maternal obesity combined with a Western-style diet (WSD) impairs offspring muscle insulin action. Adult females were fed a control or WSD prior to and during pregnancy through lactation, and offspring subsequently weaned to a control or WSD. Muscle glucose uptake and signaling were measured ex vivo in fetal (n = 5-8/group) and juvenile (n = 8/group) offspring. In vivo signaling was evaluated after an insulin bolus just prior to weaning (n = 4-5/group). Maternal WSD reduced insulin-stimulated glucose uptake and impaired insulin signaling at the level of Akt phosphorylation in fetal muscle. In juvenile offspring, insulin-stimulated glucose uptake was similarly reduced by both maternal and postweaning WSD and corresponded to modest reductions in insulin-stimulated Akt phosphorylation relative to controls. We conclude that maternal WSD leads to a persistent decrease in offspring muscle insulin-stimulated glucose uptake even in the absence of increased offspring adiposity or markers of systemic insulin resistance. Switching offspring to a healthy diet did not reverse the effects of maternal WSD on muscle insulin action, suggesting earlier interventions may be warranted.

Associations between the activity of placental nutrient-sensing pathways and neonatal and postnatal metabolic health: the ECHO Healthy Start cohort.

Our hypothesis was that the activity of placental nutrient-sensing pathways is associated with adiposity and metabolic health in childhood. Using placental villus samples from healthy mothers from the Healthy Start Study, we measured the abundance and phosphorylation of key intermediates in the mTOR, insulin, AMPK, and ER stress signaling pathways. Using multivariate multiple regression models, we tested the association between placental proteins and offspring adiposity (%fat mass) at birth (n = 109), 4-6 months (n = 104), and 4-6 years old (n = 64), adjusted for offspring sex and age. Placental mTORC1 phosphorylation was positively associated with adiposity at birth (R2 = 0.13, P = 0.009) and 4-6 years (R2 = 0.15, P = 0.046). The mTORC2 target PKCα was positively associated with systolic blood pressure at 4-6 years (β = 2.90, P = 0.005). AMPK phosphorylation was positively associated with adiposity at birth (β = 2.32, P = 0.023), but the ratio of phosphorylated to total AMPK was negatively associated with skinfold thickness (β = -2.37, P = 0.022) and body weight (β = -2.92, P = 0.005) at 4-6 years. This is the first report of associations between key placental protein activity measures and longitudinal child outcomes at various life stages. Our data indicate that AMPK and mTOR signaling are linked to cardiometabolic measures at birth and 4-6 years, providing novel insight into potential mechanisms underpinning how metabolic signaling in the placenta is associated with future risk of cardiovascular disease.

Placental function in maternal obesity.

Maternal obesity is associated with pregnancy complications and increases the risk for the infant to develop obesity, diabetes and cardiovascular disease later in life. However, the mechanisms linking the maternal obesogenic environment to adverse short- and long-term outcomes remain poorly understood. As compared with pregnant women with normal BMI, women entering pregnancy obese have more pronounced insulin resistance, higher circulating plasma insulin, leptin, IGF-1, lipids and possibly proinflammatory cytokines and lower plasma adiponectin. Importantly, the changes in maternal levels of nutrients, growth factors and hormones in maternal obesity modulate placental function. For example, high insulin, leptin, IGF-1 and low adiponectin in obese pregnant women activate mTOR signaling in the placenta, promoting protein synthesis, mitochondrial function and nutrient transport. These changes are believed to increase fetal nutrient supply and contribute to fetal overgrowth and/or adiposity in offspring, which increases the risk to develop disease later in life. However, the majority of obese women give birth to normal weight infants and these pregnancies are also associated with activation of inflammatory signaling pathways, oxidative stress, decreased oxidative phosphorylation and lipid accumulation in the placenta. Recent bioinformatics approaches have expanded our understanding of how maternal obesity affects the placenta; however, the link between changes in placental function and adverse outcomes in obese women giving birth to normal sized infants is unclear. Interventions that specifically target placental function, such as activation of placental adiponectin receptors, may prevent the transmission of metabolic disease from obese women to the next generation.

Maternal Resveratrol Treatment Re-Programs and Maternal High-Fat Diet-Induced Retroperitoneal Adiposity in Male Offspring.

Obesity during pregnancy increases the risk of cardiovascular problems, diabetes, asthma, and cognitive impairments, affecting the offspring. It is important to reduce the negative effects of obesity and high-fat (HF) diet during pregnancy. We employed a rat model of maternal HF diet to evaluate the possible de-programming effects of resveratrol in rodent male offspring with maternal HF diet/obesity. Male rat offspring were randomized into four groups: maternal control diet/postnatal control diet, maternal HF diet/postnatal control diet, maternal control diet plus maternal resveratrol treatment/postnatal control diet, and maternal HF diet plus maternal resveratrol treatment/postnatal control diet. Maternal HF diet during pregnancy plus lactation resulted in retroperitoneal adiposity in the male offspring. Maternal resveratrol treatment re-programmed maternal HF exposure-induced visceral adiposity. Offspring that received prenatal HF diet showed higher leptin/soluble leptin receptor (sOB-R) ratio than offspring that received prenatal control diet. Maternal resveratrol treatment ameliorated maternal HF exposure-induced increase in leptin/sOB-R ratio and altered the expression of genes for crucial fatty acid synthesis enzymes in the offspring. Thus, maternal resveratrol administration reduces retroperitoneal adiposity in rat offspring exposed to prenatal HF diet/obesity and could be used to ameliorate negative effects of maternal HF diet in the offspring.