Changes in PPAR-γ Expression Are Associated with microRNA Profiles during Fetal Programming due to Maternal Overweight and Obesity

2021 ◽  
pp. 1-12
Author(s):  
Noemí Gaytán-Pacheco ◽  
Victoria Lima-Rogel ◽  
Alejandro Méndez-Mancilla ◽  
Francisco Escalante-Padrón ◽  
Juan Carlos Toro-Ortíz ◽  
...  

<b><i>Background:</i></b> There has been a global increase in the prevalence of obesity in pregnant women in recent years. Animal studies have shown that intrauterine environment associated with maternal obesity leads to epigenetic changes. However, the effects of epigenetic changes occurring before birth in response to maternal conditions have not been clearly characterized in humans. <b><i>Objective:</i></b> The aim of the study was to analyze peroxisome proliferator-activated receptor (PPAR)-γ expression in cell cultures from newborns from mothers with overweight and obesity, in response to in vitro metabolic challenges and their relationship with microRNA profile and cytokine expression. <b><i>Methods/Study design:</i></b> The profile of circulating microRNAs from 72 mother-child pairs (including healthy infants born to normal weight [<i>n</i> = 35], overweight [<i>n</i> = 25], and obese [<i>n</i> = 12] mothers) was determined through real-time PCR, and the PPAR-γ expression in peripheral blood mononuclear cell cultures from offspring was analyzed after in vitro challenges. <b><i>Results:</i></b> miR-146a, miR-155, and miR-378a were upregulated in overweight mothers, while miR-378a was upregulated in obese mothers compared to normal weight mothers. In children from overweight mothers, miR-155 and miR-221 were downregulated and miR-146a was upregulated, while offspring of mothers with obesity showed downregulation of miR-155, miR-221, and miR-1301. These microRNAs have direct or indirect relation with PPAR-γ expression. In vitro exposure to high triglyceride and exposure to miR-378a induced a higher expression of PPAR-γ in cells from offspring of mothers with overweight and obesity. In contrast, cells from offspring of mothers with obesity cultured with high glucose concentrations showed PPAR-γ downregulation. IL-1ß, IL-6, and TNF-α expression in cells of offspring of overweight and obese mothers differed from that of offspring of normal weight mothers. Limitation of our study is the small sample size. <b><i>Conclusion:</i></b> The blood microRNA profile, and in vitro PPAR-γ and inflammatory cytokine expression in cells of newborn infants are associated with maternal obesity indicating that epigenetic marks may be established during intrauterine development. <b><i>Key Message:</i></b> Neonatal microRNA profile is associated with maternal weight. Neonatal microRNA profile is independent of maternal microRNA profile. PPAR-γ expression in newborn cell cultures is affected by maternal weight

Author(s):  
Eduardo Villamor ◽  
Mikael Norman ◽  
Stefan Johansson ◽  
Sven Cnattingius

Abstract Background Maternal overweight and obesity are related to risks of pregnancy and delivery complications that, in turn, are associated with newborn infections. We examined the associations between early pregnancy body mass index (BMI; kg/m2) and risk of early-onset neonatal bacterial sepsis (EOS). Methods We conducted a nationwide population-based retrospective cohort study of 1 971 346 live singleton infants born in Sweden between 1997 and 2016. Outcome was a culture-confirmed EOS diagnosis. We estimated hazard ratios (HR) of EOS according to BMI using proportional hazard models, and identified potential mediators. Among term infants, we conducted sibling-controlled analyses. Results EOS risk per 1000 live births was 1.48; 0.76 in term and 15.52 in preterm infants. Compared with infants of normal-weight mothers (BMI, 18.5–24.9), the adjusted HR (95% confidence interval [CI]) of EOS for BMI categories &lt;18.5, 25.0–29.9, 30.0–34.9, 35.0–39.9, and ≥40.0 were, respectively, 1.07 (.83–1.40), 1.19 (1.08–1.32), 1.70 (1.49–1.94), 2.11 (1.73–2.58), and 2.50 (1.86–3.38). Maternal overweight and obesity increased the risk of EOS by group B Streptococcus, Staphylococcus aureus, and Escherichia coli. Half of the association was mediated through preeclampsia, cesarean section delivery, and preterm delivery. A dose-response association was consistently apparent in term infants only. In sibling-controlled analyses, every kilogram per meter squared interpregnancy BMI change was associated with a mean 8.3% increase in EOS risk (95% CI, 1.7%–15.3%; P = .01). Conclusions Risk of EOS increases with maternal overweight and obesity severity, particularly in term infants.


2018 ◽  
Vol 48 (14) ◽  
pp. 2353-2363 ◽  
Author(s):  
Satu M. Kumpulainen ◽  
Polina Girchenko ◽  
Marius Lahti-Pulkkinen ◽  
Rebecca M. Reynolds ◽  
Soile Tuovinen ◽  
...  

AbstractBackgroundPrevious studies have linked maternal obesity with depressive symptoms during and after pregnancy. It remains unknown whether obesity associates with consistently elevated depressive symptoms throughout pregnancy, predicts symptoms postpartum when accounting for antenatal symptoms, and if co-morbid hypertensive and diabetic disorders add to these associations. We addressed these questions in a sample of Finnish women whom we followed during and after pregnancy.MethodsEarly pregnancy body mass index, derived from the Finnish Medical Birth Register and hospital records in 3234 PREDO study participants, was categorized into underweight (<18.5 kg/m2), normal weight (18.5–24.99 kg/m2), overweight (25–29.99 kg/m2), and obese (⩾30 kg/m2) groups. The women completed the Center for Epidemiological Studies Depression Scale biweekly during pregnancy, and at 2.4 (s.d.= 1.2) and/or 28.2 (s.d.= 4.2) weeks after pregnancy.ResultsIn comparison to normal weight women, overweight, and obese women reported higher levels of depressive symptoms and had higher odds of clinically significant depressive symptoms during (23% and 43%, respectively) and after pregnancy (22% and 36%, respectively). Underweight women had 68% higher odds of clinically significant depressive symptoms after pregnancy. Overweight and obesity also predicted higher depressive symptoms after pregnancy in women not reporting clinically relevant symptomatology during pregnancy. Hypertensive and diabetic disorders did not explain or add to these associations.ConclusionsMaternal early pregnancy overweight and obesity and depressive symptoms during and after pregnancy are associated. Mental health promotion should be included as an integral part of lifestyle interventions in early pregnancy obesity and extended to benefit also overweight and underweight women.


2018 ◽  
Vol 36 (05) ◽  
pp. 476-483 ◽  
Author(s):  
Esa Davis ◽  
Gregory Ewald ◽  
Michael Givertz ◽  
Navin Rajagopalan ◽  
Leslie Cooper ◽  
...  

Objective To examine the association between maternal obesity on left ventricular (LV) size and recovery in women with peripartum cardiomyopathy (PPCM). Study Design This was a prospective analysis of 100 women enrolled within 13 weeks of PPCM diagnosis and followed for a year in the Investigation of Pregnancy Associated Cardiomyopathy study. Adiposity was defined by standard body mass index (BMI) definitions for under/normal weight, overweight, and obesity. Demographic, clinical, and biomarker variables were compared across weight categories. Outcomes LV end-diastolic diameter (LVEDD) and ejection fraction were measured at entry, 6, and 12 months postpartum. Multivariable regression models examined the relationship between adiposity, LV size, and leptin levels with cardiac recovery at 6 and 12 months postpartum. Results Obese and nonobese women had similar LV dysfunction at entry. Obese women had greater LV size and less LV recovery at 6 and 12 months postpartum. BMI was positively associated with leptin and ventricular diameter. Greater BMI at entry remained associated with less ventricular recovery at 6 months (p = 0.02) in adjusted race-stratified models. LVEDD at entry predicted lower ejection fraction at 6 months (p < 0.001) and similarly at 12 months. Conclusion Obese women with PPCM had greater cardiac remodeling, higher leptin levels, and diminished cardiac recovery.


2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Song Zhang ◽  
Leewen Rattanatray ◽  
Janna L. Morrison ◽  
Lisa M. Nicholas ◽  
Shervi Lie ◽  
...  

There is a need to understand the separate or interdependent contributions of maternal prepregnancy BMI, gestational weight gain, glycaemic control, and macronutrient intake on the metabolic outcomes for the offspring. Experimental studies highlight that there may be separate influences of maternal obesity during the periconceptional period and late gestation on the adiposity of the offspring. While a period of dietary restriction in obese mothers may ablate the programming of obesity, it is associated with an activation of the stress axis in the offspring. Thus, maternal obesity may result in epigenetic changes which predict the need for efficient fat storage in postnatal life, while maternal weight loss may lead to epigenetic changes which predict later adversity. Thus, development of dietary interventions for obese mothers during the periconceptional period requires a greater evidence base which allows the effective weighing up of the metabolic benefits and costs for the offspring.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2154 ◽  
Author(s):  
Andrea de la Garza Puentes ◽  
Adrià Martí Alemany ◽  
Aida Maribel Chisaguano ◽  
Rosa Montes Goyanes ◽  
Ana I. Castellote ◽  
...  

This study analyzed how maternal obesity affected fatty acids (FAs) in breast milk and their association with infant growth and cognition to raise awareness about the programming effect of maternal health and to promote a healthy prenatal weight. Mother–child pairs (n = 78) were grouped per maternal pre-pregnancy body mass index (BMI): normal-weight (BMI = 18.5–24.99), overweight (BMI = 25–29.99) and obese (BMI > 30). Colostrum and mature milk FAs were determined. Infant anthropometry at 6, 18 and 36 months of age and cognition at 18 were analyzed. Mature milk exhibited lower arachidonic acid (AA) and docosahexaenoic acid (DHA), among others, than colostrum. Breast milk of non-normal weight mothers presented increased saturated FAs and n6:n3 ratio and decreased α-linolenic acid (ALA), DHA and monounsaturated FAs. Infant BMI-for-age at 6 months of age was inversely associated with colostrum n6 (e.g., AA) and n3 (e.g., DHA) FAs and positively associated with n6:n3 ratio. Depending on the maternal weight, infant cognition was positively influenced by breast milk linoleic acid, n6 PUFAs, ALA, DHA and n3 LC-PUFAs, and negatively affected by n6:n3 ratio. In conclusion, this study shows that maternal pre-pregnancy BMI can influence breast milk FAs and infant growth and cognition, endorsing the importance of a healthy weight in future generations.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 446
Author(s):  
Jessica L. Saben ◽  
Clark R. Sims ◽  
Ann Abraham ◽  
Lars Bode ◽  
Aline Andres

Human milk oligosaccharides (HMOs) are bioactive molecules playing a critical role in infant health. We aimed to quantify the composition of HMOs of women with normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), or obesity (30.0–60.0 kg/m2) and determine the effect of HMO intake on infant growth. Human milk (HM) samples collected at 2 months (2 M; n = 194) postpartum were analyzed for HMO concentrations via high-performance liquid chromatography. Infant HM intake, anthropometrics and body composition were assessed at 2 M and 6 M postpartum. Linear regressions and linear mixed-effects models were conducted examining the relationships between maternal BMI and HMO composition and HMO intake and infant growth over the first 6 M, respectively. Maternal obesity was associated with lower concentrations of several fucosylated and sialylated HMOs and infants born to women with obesity had lower intakes of these HMOs. Maternal BMI was positively associated with lacto-N-neotetraose, 3-fucosyllactose, 3-sialyllactose and 6-sialyllactose and negatively associated with disialyllacto-N-tetraose, disialyllacto-N-hexaose, fucodisialyllacto-N-hexaose and total acidic HMOs concentrations at 2 M. Infant intakes of 3-fucosyllactose, 3-sialyllactose, 6-sialyllactose, disialyllacto-N-tetraose, disialyllacto-N-hexaose, and total acidic HMOs were positively associated with infant growth over the first 6 M of life. Maternal obesity is associated with changes in HMO concentrations that are associated with infant adiposity.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Linda Hjertberg ◽  
Eva Uustal ◽  
Sofia Pihl ◽  
Marie Blomberg

Introduction. To evaluate if there was a difference in the anovaginal distance (AVD) measured by transperineal ultrasound between obese and normal weight women. Material and Methods. A prospective observational study including 207 primiparous women at term in first stage of labor. Transperineal ultrasound with a vaginal probe was used to measure the AVD. Maternal, pregnancy, and delivery characteristics potentially associated with perineal thickness were extracted from woman’s medical records. The participants were divided into three BMI groups based on maternal weight in early pregnancy: normal weight (BMI < 25), overweight (BMI 25–29.9), and obesity (BMI ≥ 30). Obese and overweight women were compared with normal weight women regarding the AVD. Results. The mean AVD was 24.3, 24.9, and 27.0 mm in the normal weight, overweight, and obesity group, respectively. There were no group differences in background characteristics. The AVD was significantly longer in obese women compared with normal weight women (p=0.018). Conclusions. The observed longer AVD in obese women might be protective of the anal sphincter complex, explaining lower rates of anal sphincter injuries in this group. Further studies are indicated to evaluate whether the length of the AVD plays a role in the risk assessment of obstetric anal sphincter injury. The trial is registered in ClinicalTrials.gov and the trial registration ID is NCT03149965.


2008 ◽  
Vol 11 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Pamela S Gaskin ◽  
Hedy Broome ◽  
Colin Alert ◽  
Henry Fraser

AbstractObjectivesTo describe (1) the prevalence of overweight and obesity and their association with physical activity; (2) the effect of different cut-off points for body mass index (BMI) on weight status categorisation; and (3) associations of weight status with perceptions of body size, health and diet quality.DesignA cross-sectional study.SettingSecondary schools in Barbados.SubjectsA cohort of 400 schoolchildren, 11–16 years old, selected to study physical education practices.ResultsPrevalence of overweight (15% boys; 17% girls) and obesity (7% boys; 12% girls) was high. Maternal obesity, as defined by the International Obesity Task Force (IOTF) BMI cut-off points, predicted weight status such that reporting an obese mother increased the odds of being overweight by 5.25 (95% confidence interval: 2.44, 11.31). Physical activity was inversely associated with weight status; however levels were low. Recreational physical activity was not associated with weight status in either category. Overweight subjects tended to misclassify themselves as normal weight and those who misclassified perceived themselves to be of similar health status to normal-weight subjects. The National Center for Health Statistics and IOTF BMI cut-off points produced different estimates of overweight and obesity.ConclusionsOur findings suggest that inadequate physical activity and ignorance related to food and appropriate body size are promoting high levels of adiposity with a strong contribution from maternal obesity, which may be explained by perinatal and other intergenerational effects acting on both sexes. Prevalence studies and local proxy tools for adiposity assessment are needed.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Nicole M Brunton ◽  
Allison Dart ◽  
Meghan Azad ◽  
Jonathan M McGavock

Objectives: Examine the relationship between maternal pre-pregnancy body mass index (BMI) and offspring systolic blood pressure (SBP) at 18 yrs old. Methods: We performed multivariate regression and causal mediation analysis within 3700 mother - offspring pairs from a prospective birth cohort. The main exposure was maternal pre-pregnancy BMI categorized as healthy weight, overweight, or obese according to international criteria. The main outcomes were high-normal BP and hypertension defined as SBP between the 90-95 th centile and >95 th centile for height and sex at 18 years, respectively, as per 2017 AAP guidelines. Analyses were adjusted for social class, pre-eclampsia, sex, and maternal tobacco use during pregnancy. The Canadian Pediatric Endocrine Group R Shiny app was used to obtain age-standardized BMI Z-scores and latent class analysis (LCA) was used to quantify the mediating factor of offspring BMIZ trajectories from 7 to 18 yrs. Results: Before pregnancy 14% of women were overweight and 5% were obese. At 18 yrs, SBP (122 ± 12 vs 118 ±11mmHg, p < 0.001), DBP (67 ± 7 vs 63 ± 6mmHg, p < 0.001) and the odds of elevated BP (aOR: 1.6; 95% CI: 1.1-2.3) and hypertension (aOR: 2.1; 95% CI: 1.4-3.1) were higher in offspring from women that were obese prior to pregnancy compared to those that were normal weight. LCA identified five distinct offspring BMIZ trajectories shown in the figure. SBP (125 ± 12 vs 117 ± 10 mmHg, p < 0.001) and the odds of hypertension (aOR: 3.8; 95% CI: 2.8-5.1) at 18 years were significantly higher in offspring with sustained high BMIZ (teal) compared to sustained low normal BMIZ (green). Casual mediation analysis revealed that maternal BMI directly (OR: 1.14; 95% CI: 1.03-1.25) and indirectly through offspring BMIZ trajectories (OR: 1.12; 95% CI: 1.08-1.15) increased offspring SBP at 18 years of age. Conclusion: Maternal obesity prior to pregnancy is associated with an increased risk of hypertension in offspring at 18 yrs of age, partly mediated by an elevated BMIZ score trajectory throughout childhood and adolescence.


2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Fisun Vural ◽  
Birol Vural ◽  
Yiğit Çakıroğlu

Objective. Obesity is a worldwide concern with detrimental health effects including decreased fecundity. However, obesity’s impact on in vitro fertilization (IVF) is inconclusive and there is little data concerning poor ovarian responders (POR). This study explored the effects of overweight and obesity on IVF outcomes of POR.Design. We retrospectively evaluated 188 POR undergoing IVF cycles.Methods. Patients were categorized into three groups. Group 1 was normal weight POR (18.5–24.9 kg/m2,n=96); Group 2 was overweight POR (25.0–29.9 kg/m2,n=52); and Group 3 was obese POR (≥30.0 kg/m2,n=40). Main measured outcomes included IVF outcomes.Results. The oocyte maturity, total gonadotropin dose-duration, and cycle cancellation rates were similar. Obese women had significantly decreased LH levels. LH < 4 mIU/mL had a sensitivity (62%) and a specificity (86%) for IVF failure (AUC: 0.71). Fertilization rates of obese subjects were significantly lower than normal and overweight subjects (p=0.04). Obese women’s clinical pregnancy rates were significantly lower (15%) than normal weight women (33.3%,p=0.01).Conclusions. Despite similar counts of recruited mature oocytes, obese POR women had decreased fertilization and clinical pregnancy rates. Obesity rather than overweight significantly decreased IVF outcomes in POR.


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