Parental obesity predisposes offspring to kidney dysfunction and increased susceptibility to ischemia-reperfusion injury in a sex-dependent manner.

Although obesity is recognized as a risk factor for cardiorenal and metabolic diseases, the impact of parental obesity on the susceptibility of their offspring to renal injury at adulthood is unknown. We examined the impact of parental obesity on offspring kidney function, morphology, and markers of kidney damage after acute kidney injury (AKI). Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were fed N (HN) or H diet (HH) after weaning. All offspring groups were submitted to bilateral AKI by clamping the left and right renal pedicles for 30 min. Compared with male NH and NN offspring from lean parents, male HH and HN offspring from obese parents exhibited higher kidney injury markers such as urinary, renal osteopontin, plasma creatinine, urinary albumin excretion, and neutrophil gelatinase-associated lipocalin (NGAL) levels, and worse histological injury score at 22 wk of age. Only albumin excretion and NGAL were elevated in female HH offspring from obese parents compared with lean and obese offspring from lean parents. We also found an increased mortality rate and worse kidney injury scores after AKI in male offspring from obese parents, regardless of the diet consumed after weaning. Female offspring were protected from major kidney injury after AKI. These results indicate that parental obesity leads to increased kidney injury in their offspring after ischemia-reperfusion in a sex-dependent manner, even when their offspring remain lean.NEW & NOTEWORTHY Offspring from obese parents are more susceptible to kidney injury and worse outcomes following an acute ischemia-reperfusion insult. Male, but not female, offspring from obese parents exhibit increased blood pressure early in life. Female offspring are partially protected against major kidney injury induced by ischemia-reperfusion.

Maternal diet-induced obesity during pregnancy alters lipid supply to mouse E18.5 fetuses and changes the cardiac tissue lipidome in a sex-dependent manner.

Maternal obesity during pregnancy has immediate and long-term detrimental effects on the offspring heart. In this study, we characterized the cardiac and circulatory lipid profiles in late gestation E18.5 fetuses of diet-induced obese pregnant mice and established the changes in lipid abundance and fetal cardiac transcriptomics. We used untargeted and targeted lipidomics and transcriptomics to define changes in the serum and cardiac lipid composition and fatty acid metabolism in male and female fetuses. From these analyses we observed: (1) maternal obesity affects the maternal and fetal serum lipidome distinctly; (2) female fetal heart lipidomes are more sensitive to maternal obesity than males; (3) changes in lipid supply might contribute to early expression of lipolytic genes in mouse hearts exposed to maternal obesity. These results highlight the existence of sexually dimorphic responses of the fetal heart to the same in utero obesogenic environment and identify lipids species that might mediate programming of cardiovascular health.

Maternal pre-pregnancy BMI associates with neonate local and distal functional connectivity of the left superior frontal gyrus.

Maternal obesity/overweight during pregnancy has reached epidemic proportions and has been linked with adverse outcomes for the offspring, including cognitive impairment and increased risk for neuropsychiatric disorders. Prior neuroimaging investigations have reported widespread aberrant functional connectivity and white matter tract abnormalities in neonates born to obese mothers. Here we explored whether maternal pre-pregnancy adiposity is associated with alterations in local neuronal synchrony and distal connectivity in the neonate brain. 21 healthy mother-neonate dyads from uncomplicated pregnancies were included in this study (age at scanning 26.14 ± 6.28 days, 12 male). The neonates were scanned with a 6-min resting-state functional magnetic resonance imaging (rs-fMRI) during natural sleep. Regional homogeneity (ReHo) maps were computed from obtained rs-fMRI data. Multiple regression analysis was performed to assess the association of pre-pregnancy maternal body-mass-index (BMI) and ReHo. Seed-based connectivity analysis with multiple regression was subsequently performed with seed-ROI derived from ReHo analysis. Maternal adiposity measured by pre-pregnancy BMI was positively associated with neonate ReHo values within the left superior frontal gyrus (SFG) (FWE-corrected p < 0.005). Additionally, we found both positive and negative associations (p < 0.05, FWE-corrected) for maternal pre-pregnancy BMI and seed-based connectivity between left SFG and prefrontal, amygdalae, basal ganglia and insular regions. Our results imply that maternal pre-pregnancy BMI associates with local and distal functional connectivity within the neonate left superior frontal gyrus. These findings add to the evidence that increased maternal pre-pregnancy BMI has a programming influence on the developing neonate brain functional networks.

Association of maternal obesity with fetal and neonatal death: Evidence from South and South-East Asian countries.

BACKGROUND: Obesity prevalence is increasing in many countries in the world, including Asia. Maternal obesity is highly associated with fetal and neonatal deaths. This study investigated whether maternal obesity is a risk factor of fetal death (measured in terms of miscarriage and stillbirth) and neonatal mortality in South and South-East Asian countries. METHODS: This cross-sectional study pooled the most recent Demographic and Health Surveys (DHS) from eight South and South-East Asian countries (2014-2018). Multivariate logistic regression was deployed to check the relationships between maternal obesity with fetal and neonatal deaths. Finally, multilevel logistic regression model was employed since the DHS data has a hierarchical structure. RESULTS: The pooled logistic regression model illustrated that maternal obesity is associated with higher odds of miscarriage (adjusted odds ratio [aOR]: 1.26, 95% CI: 1.20-1.33) and stillbirths (aOR: 1.46, 95% CI: 1.27-1.67) after adjustment of confounders. Children of obese mothers were at 1.18 (aOR: 1.18, 95% CI: 1.08-1.28) times greater risk of dying during the early neonatal period than mothers with a healthy weight. However, whether maternal obesity is statistically a significant risk factor for the offspring's late neonatal deaths was not confirmed. The significant association between maternal obesity with miscarriage, stillbirth and early neonatal mortality was further confirmed by multilevel logistic regression results. CONCLUSION: Maternal obesity in South and South-East Asian countries is associated with a greater risk of fetal and early neonatal deaths. This finding has substantial public health implications. Strategies to prevent and reduce obesity should be developed before planning pregnancy to reduce the fetal and neonatal death burden. Obese women need to deliver at the institutional facility centre that can offer obstetrics and early neonatal care.

Investigation of optimal gestational weight gain based on the occurrence of adverse pregnancy outcomes for Chinese women: a prospective cohort study.

OBJECTIVE: To investigate recommendations for appropriate gestational weight gain (GWG) of Chinese females. METHODS: In total of 3,172 eligible women in the first trimester were recruited into the Chinese Pregnant Women Cohort Study (CPWCS) project. Pregnancy complications and outcomes were collated using the hospital medical records system. The method of occurrence of participants with adverse pregnancy outcomes (Occurrence Method) was conducted to calculate the recommended total GWG for each participant's pre-pregnancy BMI. Occurrence Method data were judged against the Institute of Medicine (IOM) and Japanese recommended criteria in terms of the total occurrence of adverse pregnancy outcomes of pregnant women with appropriate weight gain. RESULTS: The most frequent GWG was ≥ 14 kg and < 16 kg (19.4%), followed by ≥ 10 kg and < 12 kg (15.5%) and ≥ 12 kg and < 14 kg (15.2%). The most frequently occurring adverse pregnancy outcomes were cesarean sections for underweight (30.0%), normal weight (40.4%), overweight (53.6%) and obese (53.7%) women. A large for gestational age (LGA) accounted for 18.0% of the overweight and 20.9% of the obesity group. Gestational diabetes mellitus (GDM) occurred in 16.9% of overweight and 23.1% of obese women. The recommended total GWG in a Chinese women population is ≥ 8 and < 12 kg if underweight, ≥ 12 and < 14 kg for normal weight, ≥ 8.0 and < 10.0 kg if overweight, and < 8 kg for women with obesity. CONCLUSIONS: Current Chinese recommendations provide the optimal ranges of GWG to minimize the occurrence of undesirable pregnancy outcomes for each group of pre-pregnancy BMIs in a Chinese population. TRIAL REGISTRATION: Registered with ClinicalTrials ( NCT03403543 ).

Effect of Polyphenols Intake on Obesity-Induced Maternal Programming.

Excess caloric intake and body fat accumulation lead to obesity, a complex chronic disease that represents a significant public health problem due to the health-related risk factors. There is growing evidence showing that maternal obesity can program the offspring, which influences neonatal phenotype and predispose offspring to metabolic disorders such as obesity. This increased risk may also be epigenetically transmitted across generations. Thus, there is an imperative need to find effective reprogramming approaches in order to resume normal fetal development. Polyphenols are bioactive compounds found in vegetables and fruits that exert its anti-obesity effect through its powerful anti-oxidant and anti-inflammatory activities. Polyphenol supplementation has been proven to counteract the prejudicial effects of maternal obesity programming on progeny. Indeed, some polyphenols can cross the placenta and protect the fetal predisposition against obesity. The present review summarizes the effects of dietary polyphenols on obesity-induced maternal reprogramming as an offspring anti-obesity approach.

Obesity Challenge Drives Distinct Maternal Immune Response Changes in Normal Pregnant and Abortion-Prone Mouse Models.

Obesity is prevalent among women of reproductive age and is associated with increased risk of developing multiple pregnancy disorders. Pregnancy must induce immune tolerance to avoid fetal rejection, while obesity can cause chronic inflammation through activating the immune system. Impaired maternal immuno-tolerance leads to pregnancy failure, such as recurrent spontaneous abortion (RSA), one of the most common complications during early pregnancy. How does maternal immune response change under obesity stress in normal pregnancy and RSA? In turn, is obesity affected by different gestational statuses? Limited information is presently available now. Our study investigated pregnancy outcomes and maternal immune responses in two murine models (normal pregnancy and spontaneous abortion models) after obesity challenge with a high-fat diet (HFD). Abortion-prone mice fed HFD had significantly higher weight gains during pregnancy than normal pregnant mice with HFD feeding. Nonetheless, the embryo implantation and resorption rates were comparable between HFD and normal chow diet (NCD)-fed mice in each model. Evaluation of immune cell subsets showed HFD-induced obesity drove the upregulation of activated NK cell-activating receptor (NKp46)+ NK cells and pro-inflammatory macrophages (MHCIIhigh Mφ) as well as CD4+ and CD8+ T cells in the normal pregnancy group. However, in the abortion-prone group, relative more immature NK cells with decreased activity phenotypes were found in obese mice. Moreover, there were increased DCreg (CD11bhigh DC) cells and decreased CD4+ and CD8+ T cells detected in the HFD abortion-prone mice relative to those fed the NCD diet. Our findings reveal how pregnancy obesity and maternal immune regulation are mutually influenced. It is worth noting that the abortion-prone model where active maternal immune status was intensified by obesity, in turn stimulated an overcompensation response, leading to an over-tolerized immune status, and predisposing to potential risks of perinatal complications.

Maternal Exercise Mediates Hepatic Metabolic Programming via Activation of AMPK-PGC1α Axis in the Offspring of Obese Mothers.

Maternal obesity is associated with an increased risk of hepatic metabolic dysfunction for both mother and offspring and targeted interventions to address this growing metabolic disease burden are urgently needed. This study investigates whether maternal exercise (ME) could reverse the detrimental effects of hepatic metabolic dysfunction in obese dams and their offspring while focusing on the AMP-activated protein kinase (AMPK), representing a key regulator of hepatic metabolism. In a mouse model of maternal western-style-diet (WSD)-induced obesity, we established an exercise intervention of voluntary wheel-running before and during pregnancy and analyzed its effects on hepatic energy metabolism during developmental organ programming. ME prevented WSD-induced hepatic steatosis in obese dams by alterations of key hepatic metabolic processes, including activation of hepatic ß-oxidation and inhibition of lipogenesis following increased AMPK and peroxisome-proliferator-activated-receptor-γ-coactivator-1α (PGC-1α)-signaling. Offspring of exercised dams exhibited a comparable hepatic metabolic signature to their mothers with increased AMPK-PGC1α-activity and beneficial changes in hepatic lipid metabolism and were protected from WSD-induced adipose tissue accumulation and hepatic steatosis in later life. In conclusion, this study demonstrates that ME provides a promising strategy to improve the metabolic health of both obese mothers and their offspring and highlights AMPK as a potential metabolic target for therapeutic interventions.

Influence of maternal body mass index on interobserver variability of fetal ultrasound biometry and amniotic-fluid assessment in late pregnancy.

OBJECTIVE: To determine the interobserver reproducibility of fetal ultrasound biometric and amniotic-fluid measurements in the third trimester of pregnancy, according to maternal body mass index (BMI) category. METHODS: This was a prospective cohort study of women with a singleton gestation beyond 34 weeks, recruited into four groups according to BMI category: normal (18.0-24.9 kg/m2 ), overweight (25.0-29.9 kg/m2) , obese (30.0-39.9 kg/m2 ) and morbidly obese (≥ 40 kg/m2 ). Multiple pregnancies, women with diabetes and pregnancies with a fetal growth, structural or genetic abnormality were excluded. In each woman, fetal biometric (biparietal diameter (BPD), head circumference, abdominal circumference (AC), femur length (FL) and estimated fetal weight) and amniotic-fluid (amniotic-fluid index (AFI) and maximum vertical pocket (MVP)) measurements were obtained by two experienced sonographers or physicians, blinded to gestational age and each other's measurements. Differences in measurements between observers were expressed as gestational age-specific Z-scores. The interobserver intraclass correlation coefficient (ICC) and Cronbach's reliability coefficient (CRC) were calculated. Bland-Altman analysis was used to assess the degree of reproducibility. RESULTS: In total, 110 women were enrolled prospectively (including 1320 measurements obtained by 17 sonographers or physicians). Twenty (18.2%) women had normal BMI, 30 (27.3%) women were overweight, 30 (27.3%) women were obese and 30 (27.3%) women were morbidly obese. Except for AFI (ICC, 0.65; CRC, 0.78) and MVP (ICC, 0.49; CRC, 0.66), all parameters had a very high level of interobserver reproducibility (ICC, 0.72-0.87; CRC, 0.84-0.93). When assessing reproducibility according to BMI category, BPD measurements had a very high level of reproducibility (ICC ≥ 0.85; CRC > 0.90) in all groups. The reproducibility of AC and FL measurements increased with increasing BMI, while the reproducibility of MVP measurements decreased. Among the biometric parameters, the difference between the BMI categories in measurement-difference Z-score was significant only for FL. Interobserver differences for biometric measurements fell within the 95% limits of agreement. CONCLUSION: Obesity does not seem to impact negatively on the reproducibility of ultrasound measurements of fetal biometric parameters when undertaken by experienced sonographers or physicians who commonly assess overweight, obese and morbidly obese women. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

The INTER-ACT E-Health Supported Lifestyle Intervention Improves Postpartum Food Intake and Eating Behavior, but Not Physical Activity and Sedentary Behavior-A Randomized Controlled Trial.

Unhealthy postpartum lifestyle is related to long-term adverse psychological, metabolic and cardiovascular health outcomes as well as to complications in the next pregnancy. Especially women with preceding excessive gestational weight gain are at risk. This paper aims to evaluate the effect of the postpartum phase of the INTER-ACT randomized controlled trial (RCT) on food intake, eating behavior, physical activity and sedentary time at the end of the intervention (six months postpartum) and at six-months follow-up (12 months postpartum). The study population comprised women with excessive gestational weight gain in the preceding pregnancy. The lifestyle intervention combined a smartphone application with four face-to-face coaching sessions between six weeks and six months postpartum. After the intervention, restrained eating score was 1 point higher (95% CI 0.5, 1.5; p < 0.001), uncontrolled eating score was 1 point lower (95% CI -1.9, -0.2; p = 0.02) and energy intake was 69 kcal lower (95% CI -123, -15; p = 0.01) in the intervention group compared to the control group. The differences were no longer statistically significant at follow-up. No significant effects on emotional eating, physical activity and sedentary behavior were found. In conclusion, the postpartum phase of the INTER-ACT RCT was effective in improving nutrition-related outcomes, however, these improvements could not be sustained at follow-up. ClinicalTrials.gov identifier: NCT02989142.

Low Resting Energy Expenditure Is Associated with High Gestational Weight Gain Only When Resting Energy Expenditure Fluctuates.

Resting energy expenditure (REE) may be useful for individualizing energy intake (EI) and physical activity (PA) goals, and in turn, regulating gestational weight gain (GWG). Limited research, however, has examined the association between REE and GWG. This study examined (1) change in REE from 14 to 28 gestation, (2) time-varying associations between REE and GWG, and (3) EI and PA patterns during the weeks when REE and GWG were significantly associated. Pregnant women with overweight/obesity (N = 27) participating in the Healthy Mom Zone study completed weekly point estimates of EI (back-calculation), PA (wrist-worn activity monitor), REE (mobile metabolism device), and weight (Wi-Fi scale) from 14 to 28 weeks gestation. Analyses included descriptives and time-varying effect modeling. REE fluctuated, increasing on average from 14 to 28 weeks gestation, but decreased at gestational weeks 17, 20, 21, 23, 26, and 28. Most women increased in REE; however there was large between-person variability in the amount of change. Associations between REE and GWG were small but time-varying; low REE was associated with high GWG between gestational weeks 25 to 28 when there was observably larger fluctuation in REE. Moreover, over half of the women were categorized as having excessive EI and most as low active during this time. EI needs may be overestimated and PA needs may be underestimated when REE is fluctuating, which may increase the risk for high second trimester GWG. Researchers should consider the role of REE to inform EI and PA goals to regulate GWG.

The Interactive Effect of Prepregnancy Overweight/Obesity and Isolated Maternal Hypothyroxinemia on Macrosomia.

CONTEXT: Prepregnancy overweight/obesity (OWO) and isolated maternal hypothyroxinemia (IMH) may increase the risk of macrosomia, but little is known about their potential combined effect on macrosomia. OBJECTIVE: The aim of this study was to assess whether prepregnancy OWO and first-trimester IMH have a synergistic effect on the risk of macrosomia. METHODS: A large prospective cohort study in a Chinese population from January 2016 to December 2018 in a tertiary care center. In total, 34 930 pregnant women were included. The main outcome measure was macrosomia. RESULTS: A total of 34 930 participants comprising IMH and euthyroid cases was included in this study. Prepregnancy OWO and first-trimester IMH were independently associated with an increased risk of macrosomia (adjusted odds ratio [OR] 2.48, 95% CI 2.22, 2.78, and adjusted OR 1.65, 95% CI 1.34, 2.01, respectively). The coexistence of prepregnancy OWO and IMH was associated with macrosomia, with an adjusted OR of 5.26 (95% CI 3.9, 7.0) compared with pregnant women without either condition. The additive interaction between prepregnancy OWO and IMH was found to be significant with regard to macrosomia. CONCLUSION: Prepregnancy OWO and IMH in the first trimester may synergistically increase the risk of macrosomia.

Pathophysiological adaptations of resistance arteries in rat offspring exposed in utero to maternal obesity is associated with sex-specific epigenetic alterations.

BACKGROUND/OBJECTIVES: Maternal obesity impacts vascular functions linked to metabolic disorders in offspring, leading to cardiovascular diseases during adulthood. Even if the relation between prenatal conditioning of cardiovascular diseases by maternal obesity and vascular function begins to be documented, little is known about resistance arteries. They are of particular interest because of their specific role in the regulation of local blood flow. Then our study aims to determine if maternal obesity can directly program fetal vascular dysfunction of resistance arteries, independently of metabolic disorders. METHODS: With a model of rats exposed in utero to mild maternal diet-induced obesity (OMO), we investigated third-order mesenteric arteries of 4-month old rats in absence of metabolic disorders. The methylation profile of these vessels was determined by reduced representation bisulfite sequencing (RRBS). Vascular structure and reactivity were investigated using histomorphometry analysis and wire-myography. The metabolic function was evaluated by insulin and glucose tolerance tests, plasma lipid profile, and adipose tissue analysis. RESULTS: At 4 months of age, small mesenteric arteries of OMO presented specific epigenetic modulations of matrix metalloproteinases (MMPs), collagens, and potassium channels genes in association with an outward remodeling and perturbations in the endothelium-dependent vasodilation pathways (greater contribution of EDHFs pathway in OMO males compared to control rats, and greater implication of PGI2 in OMO females compared to control rats). These vascular modifications were detected in absence of metabolic disorders. CONCLUSIONS: Our study reports a specific methylation profile of resistance arteries associated with vascular remodeling and vasodilation balance perturbations in offspring exposed in utero to maternal obesity, in absence of metabolic dysfunctions.

Breast milk apelin level increases with maternal obesity and high-fat feeding during lactation.

OBJECTIVE: Recent evidence indicates that levels of breast milk (BM) hormones such as leptin can fluctuate with maternal adiposity, suggesting that BM hormones may signal maternal metabolic and nutritional environments to offspring during postnatal development. The hormone apelin is highly abundant in BM but its regulation during lactation is completely unknown. Here, we evaluated whether maternal obesity and overnutrition impacted BM apelin and leptin levels in clinical cohorts and lactating rats. METHODS: BM and plasma samples were collected from normal-weight and obese breastfeeding women, and from lactating rats fed a control or a high fat (HF) diet during lactation. Apelin and leptin levels were assayed by ELISA. Mammary gland (MG) apelin expression and its cellular localization in lactating rats was measured by quantitative RT-PCR and immunofluorescence, respectively. RESULTS: BM apelin levels increased with maternal BMI, whereas plasma apelin levels decreased. BM apelin was also positively correlated with maternal insulin and C-peptide levels. In rats, maternal HF feeding exclusively during lactation was sufficient to increase BM apelin levels and decrease its plasma concentration without changing body weight. In contrast, BM leptin levels increased with maternal BMI in humans, but did not change with maternal HF feeding during lactation in rats. Apelin is highly expressed in the rat MG during lactation and was mainly localized to mammary myoepithelial cells. We found that MG apelin gene expression was up-regulated by maternal HF diet and positively correlated with BM apelin content and maternal insulinemia. CONCLUSIONS: Our study indicates that BM apelin levels increase with long- and short-term overnutrition, possibly via maternal hyperinsulinemia and transcriptional upregulation of MG apelin expression in myoepithelial cells. Apelin regulates many physiological processes, including energy metabolism, digestive function, and development. Further studies are needed to unravel the consequences of such changes in offspring development.

Maternal obesity increases the risk of fetal cardiac dysfunction via visceral adipose tissue derived exosomes.

INTRODUCTION: There is a strong association between gestational obesity and fetal cardiac dysfunction, while the exact mechanisms remain largely unknown. The purpose of this study was to investigate the role of exosomes from maternal visceral adipose tissue in abnormal embryonic development in obese pregnancy. METHODS: Female C57BL/6J obese mice were induced by a high-fat diet (containing 60% fat). Fetal cardiac function and morphology were examined by echocardiography and histology. The placenta was extracted for histological examination. miRNA expression in exosomes from the visceral adipose tissue was profiled by RNA-seq. Gene expression of inflammatory factors was analyzed by qPCR. RESULTS: In the obese pregnant mice, there were obvious inflammation and lipid droplets in the placenta. And the fetal cardiac function in obese pregnancy was also compromised. Moreover, injection of the visceral adipose tissue exosomes from the obese mice significantly decreased the fetal cardiac function in the normal lean pregnant mice. Mechanistically, the decreased expression of miR-19b might be responsible for the enhanced inflammation in the placenta. DISCUSSION: Exosomes derived from visceral adipose tissue in obese mice contribute to fetal heart dysfunction, at least partially via affecting the function of the placenta.

N-acetylcysteine protects neonatal mice from ventricular hypertrophy induced by maternal obesity in a sex-specific manner.

BACKGROUND: Maternal obesity induces adverse cardiac programming in offspring, and effective interventions are needed to prevent cardiovascular ill-health. Herein we hypothesized that exposure to maternal obesogenic diet-induced obesity in mice results in left ventricular remodelling and hypertrophy in early childhood, and that maternal N-acetylcysteine (NAC) treatment alleviates these effects in a sex-dependent manner. METHODS AND RESULTS: The maternal obesity was induced in mice by the consumption of a Western diet accompanied by a 20 % sucrose solution. To determine the effect of NAC on the cardiac outcomes induced by maternal obesity, obese dams were continuously exposed to the obesogenic diet, with or without the oral NAC treatment during pregnancy. Left ventricular remodelling and hypertrophy occurred as early as 7 days after birth in the male offspring of obese dams (O-OB) compared with controls (O-CO). An over-expression of key genes and markers related to cardiac fibrosis accompanied by more disorganized myofibrils was observed in the hearts of neonatal male O-OB mice. When we next evaluated the level of oxidative stress in the hearts of neonatal mice, the activity of enzymatic antioxidants declined and expression of NOX enzyme complex was up-regulated in O-OB offspring hearts, but was normal in the offspring of NAC treated mice (O-OB/NAC). Maternal obesity also activated cardiac Akt and mammalian target of rapamycin (mTOR) signalling in offspring, and NAC treatment restored offspring cardiac Akt-mTOR signalling to normal irrespective of sex. NAC treatment did not prevent cardiomyocyte hypertrophy but did alleviate increased heart weight, interventricular septal thickness, and collagen content in male O-OB/NAC pups. CONCLUSIONS: Collectively, our results indicated that NAC blunted cardiac fibrosis and related ventricular hypertrophy of male neonatal offspring in the setting of maternal obesity, potentially acting by reducing oxidative stress. The present study provides a basis for investigating the role of NAC in nutrition-related cardiac programming.

Inflammasomes in the Pathophysiology of Maternal Obesity: Potential Therapeutic Targets to Reduce Long-Term Adverse Health Outcomes in the Mother and Offspring.

Over the past 20 years, the prevalence of obesity has risen dramatically worldwide, with an increase in occurrence among women in their reproductive age. Obesity during pregnancy is associated with significantly increased maternal and fetal morbidity and mortality. In addition to the short-term adverse health outcomes, both mother and the child are prone to develop cardiovascular, metabolic and neurological disorders. Although associations between obesity during pregnancy and adverse maternalfetal health outcomes are clear, the complex molecular mechanisms underlying maternal obesity remain largely unknown. This review describes multimeric self-assembling protein complexes, namely inflammasomes, as potential molecular targets in the pathophysiology of maternal obesity. Inflammasomes are implicated in both normal physiological and in pathophysiological processes that occur in response to an inflammatory milieu throughout gestation. This review highlights the current knowledge of inflammasome expression and its activity in pregnancies affected by maternal obesity. Key discussions in defining pharmacological inhibition of upstream as well as downstream targets of the inflammasome signaling cascade; and the inflammasome platform, as a potential therapeutic strategy in attenuating the pathophysiology underpinning inflammatory component in maternal obesity are presented herein.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions.

Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

Effects of Maternal Obesity On Placental Phenotype.

The incidence of obesity is rising rapidly worldwide with the consequence that more women are entering pregnancy overweight or obese. This leads to an increased incidence of clinical complications during pregnancy and of poor obstetric outcomes. The offspring of obese pregnancies are often macrosomic at birth although there is also a subset of the progeny that are growth-restricted at term. Maternal obesity during pregnancy is also associated with cardiovascular, metabolic and endocrine dysfunction in the offspring later in life. As the interface between the mother and fetus, the placenta has a central role in programming intrauterine development and is known to adapt its phenotype in response to environmental conditions such as maternal undernutrition and hypoxia. However, less is known about placental function in the abnormal metabolic and endocrine environment associated with maternal obesity during pregnancy. This review discusses the placental consequences of maternal obesity induced either naturally or experimentally by increasing maternal nutritional intake and/or changing the dietary composition. It takes a comparative, multi-species approach and focusses on placental size, morphology, nutrient transport, metabolism and endocrine function during the later stages of obese pregnancy. It also examines the interventions that have been made during pregnancy in an attempt to alleviate the more adverse impacts of maternal obesity on placental phenotype. The review highlights the potential role of adaptations in placental phenotype as a contributory factor to the pregnancy complications and changes in fetal growth and development that are associated with maternal obesity.