Early growth response protein-1 mediates lipotoxicity-associated placental inflammation: role in maternal obesity

Saben, Jessica; Zhang, Ying; Gómez-Acevedo, Horacio; Thakali, Keshari; Borengasser, Sarah J.; Andres, Aline; Shankar, Kartik

doi:10.1152/ajpendo.00076.2013

Cited by 75 publications

(83 citation statements)

References 81 publications

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“…41 The mechanisms underlying maternal programming of offspring adiposity are still unclear One potential explanation may be a proinflammatory intrauterine environment promoted by maternal obesity, the resulting lipotoxicity can alter fetal development pathways via dysregulation of redox balance in the mother-placentafetus unit, which serves as one of the key downstream mediators that initiate programming of the offspring. 42,43 The mechanisms responsible for the reported sexual dimorphism in offspring adiposity as consequence of maternal overnutrition are unknown. In experimental models, strong maternal programming of adiposity in male offspring but not in female offspring was described.…”

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confidence: 99%

Low Adherence to Mediterranean Diet in Portugal: Pregnant Women Nutrition in Portugal and its Repercussions

Pereira‐da‐Silva

Pinto

2016

Acta Med Port

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Introduction: Portuguese population is drifting away from the Mediterranean diet-like pattern. In this context, the current nutritional status of women of childbearing age and of pregnant Portuguese women and their growing fetuses is critically reviewed. Material and Methods: A narrative critical review was performed on recent published high quality studies assessing diet and nutritional status of women of childbearing age and pregnant women and its influence on the nutritional status of their offspring. Results: Data from five multinational ecological studies that included Portugal, two national official surveys on food availability, seven national studies on the diet and nutritional status of women of childbearing age and pregnant women, and five national studies on the effect of nutritional maternal factors on their growing fetuses were selected and analyzed. The prevalence of overweight/obesity has dramatically increased in Portuguese women of childbearing age and pregnant women, associated with the described trend of low adherence to Mediterranean diet. Variations in energy and macronutrients intakes during pregnancy seem to have no significantly impact on the nutritional status of growing fetuses. On contrary, pre-pregnancy overweight/obesity has been associated with increased offspring adiposity at birth, and an excessive gestational weight gain may be associated with offspring's overweight status in childhood.Factors potentially contributing to low adherence to the Mediterranean diet, deserving further investigation, include European Union agriculture policies that have implemented the production of non-Mediterranean food groups at low cost, and insufficient financial capacity to afford foods of quality reported by Portuguese population. Material e Métodos:Realizámos uma revisão narrativa crítica de estudos recentes com qualidade e inquéritos nacionais oficiais, que tivessem avaliado a dieta e estado de nutrição de mulheres em idade fértil e de grávidas portuguesas e sua influência no estado de nutrição dos respetivos fetos e recém-nascidos. Resultados:Foram selecionados e analisados cinco estudos ecológicos multinacionais que incluíram Portugal, dois inquéritos oficiais nacionais sobre disponibilidade de alimentos, sete estudos nacionais sobre dieta e estado de nutrição de mulheres em idade fértil e grávidas e cinco estudos nacionais sobre a influência de fatores nutricionais maternos no crescimento dos fetos. A prevalência de excesso de peso/obesidade em mulheres em idade fértil e grávidas aumentou substancialmente associada à diminuição da adesão à dieta mediterrânica. As variações no consumo de energia e macronutrientes na gravidez parecem não ter impacto significativo no estado de nutrição dos fetos. Pelo contrário, o excesso de peso/obesidade pré-concecional associa-se a aumento de adiposidade ao nascer e o excessivo aumento de peso na gravidez associa-se ao excesso ponderal na infância. Os fatores potencialmente relacionados com a baixa adesão à dieta mediterrânica, merecendo futura inves...

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confidence: 99%

Low Adherence to Mediterranean Diet in Portugal: Pregnant Women Nutrition in Portugal and its Repercussions

Pereira‐da‐Silva

Pinto

2016

Acta Med Port

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“…Purified RNA (5 g) was used to synthesize both first-and second-strand cDNA, and double-stranded cDNA was synthesized into labeled cRNA using the GeneChip IVT labeling kit (Affymetrix) according to the manufacturer's protocol. Microarrays were scanned using a GeneChip Scanner 3000 (Affymetrix), and .CEL files were generated using GeneChip Command Console (Affymetrix) (8,49,55). GeneSpring version 11 software (Agilent Technologies, Santa Clara, CA) was used to perform data analyses.…”

Section: Methodsmentioning

confidence: 99%

“…Raw data is accessible in the NCBI GEO database (GSE76002). Probe level intensities from .CEL files were processed using robust multiarray analysis algorithm for normalization, background adjustment, and log2-transformation of perfect match values (8,49,55). Genes were filtered based on Ϯ1.3-fold change and P value Յ 0.05 (Student's t-test) between obese and lean dams.…”

Section: Methodsmentioning

confidence: 99%

“…Finally, ingenuity pathway analysis and gene set enrichment analysis (GSEA) were utilized to identify top interacting networks and biological processes enriched by maternal obesity. Gene set enrichment analysis does not rely on an arbitrary cutoff, such as fold change between groups, and is a computational method that determines whether an a priori-defined set of genes shows concordant differences and statistical significance between two biological states (8,49).…”

Section: Methodsmentioning

confidence: 99%

“…This model allows for the study of excess caloric intake without necessitating macronutrient imbalance as a potential confounder. Previous studies using this model have demonstrated a placental and uterine proinflammatory response in obese dams compared with lean controls (49,55,58). Early growth response 1 (Egr-1) was identified as a proinflammatory regulator at the placental level.…”

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confidence: 92%

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Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1

Ruebel

Shankar

Gaddy

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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A. Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1. Am J Physiol Endocrinol Metab 311: E269 -E277, 2016. First published June 7, 2016 doi:10.1152/ajpendo.00524.2015.-Obesity impairs reproductive functions through multiple mechanisms, possibly through disruption of ovarian function. We hypothesized that increased adiposity will lead to a proinflammatory gene signature and upregulation of Egr-1 protein in ovaries from obese (OB; n ϭ 7) compared with lean (LN; n ϭ 10) female Sprague-Dawley rats during the peri-implantation period at 4.5 days postcoitus (dpc). Obesity was induced by overfeeding (40% excess calories for 28 days) via total enteral nutrition prior to mating. OB dams had higher body weight (P Ͻ 0.001), greater fat mass (P Ͻ 0.001), and reduced lean mass (P Ͻ 0.05) and developed metabolic dysfunction with elevated serum lipids, insulin, leptin, and CCL2 (P Ͻ 0.05) compared with LN dams. Microarray analyses identified 284 differentially expressed genes between ovaries from LN vs. OB dams (Ϯ1.3 fold, P Ͻ 0.05). RT-qPCR confirmed a decrease in expression of glucose transporters GLUT4 and GLUT9 and elevation of proinflammatory genes, including CCL2, CXCL10, CXCL11, CCR2, CXCR1, and TNF␣ in ovaries from OB compared with LN (P Ͻ 0.05). Protein levels of PI3K and phosphorylated Akt were significantly decreased (P Ͻ 0.05), whereas nuclear levels of Egr-1 (P Ͻ 0.05) were increased in OB compared with LN ovaries. Moreover, Egr-1 was localized to granulosa cells, with the highest expression in cumulus cells of preovulatory follicles. mRNA expression of VCAN, AURKB, and PLAT (P Ͻ 0.05) correlated with %visceral fat weight (r ϭ 0.51, Ϫ0.77, and Ϫ0.57, respectively, P Յ 0.05), suggesting alterations in ovarian function with obesity. In summary, maternal obesity led to an upregulation of inflammatory genes and Egr-1 expression in peri-implantation ovarian tissue and a concurrent downregulation of GLUTs and Akt and PI3K protein levels.early growth response factor 1; gene expression; inflammation; obesity; reproduction IN THE US, 60% OF WOMEN OF REPRODUCTIVE AGE are either overweight or obese, which predisposes them to higher risk of infertility and pregnancy complications (12,21,57,59,60) and potentially leads to adverse effects on offspring development. Higher adiposity leads to hormonal dysregulation, decreased primordial follicle numbers at the initiation of follicular development, lower ovulation rates, a reduced number of cleaved blastocysts developing to eight cell stage and reduced implantation rates, and ultimately impaired reproductive function (11,16,17,22,33,35,61). Similarly, in experimental models, obesity leads to decreased primordial and preovulatory follicle numbers, increased follicular atresia and changes in steroidogenesis via decreased steroidogenic acute regulatory protein, and increased Cyp11a1 protein content in ovarian tissue (7,16,23,37,38,53,61). Evidence of lipid accumulation, endoplasmic reticulum stress, and oxidative stress in ova...

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Longitudinal body composition of children born to mothers with normal weight, overweight, and obesity

Andres

Hull

Shankar

et al. 2015

Obesity

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Objective: The longitudinal trajectories of body composition of children born to mothers with normal weight, overweight, and obesity have not been evaluated using precise body composition methods. This study investigated the relationship between maternal prepregnancy BMI and offspring body composition trajectories during the first 6 years of life. Methods: Healthy infants (N 5 325) were assessed longitudinally (at ages 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, and 6 years) using dual-energy X-ray absorptiometry. Mixed-effects regression for repeated measures was used to model each continuous outcome as a function of maternal BMI and covariates (race, gestational age, birth weight, and mode of infant feeding).Results: Maternal obesity differentially impacted body fat, but not bone mineral content or density, of girls and boys. Boys born to mothers with obesity have higher body fat from ages 2-6 years compared to boys born to normal-weight and overweight mothers (P < 0.05), whereas body composition of girls born to mothers with obesity was not different across groups during the first 6 years of life (P > 0.05).Conclusions: This clinical observational study demonstrates a sexual dimorphism in offspring body composition until age 6 years based on maternal BMI, with a greater effect of maternal adiposity seen in boys than in girls.

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Early growth response protein-1 mediates lipotoxicity-associated placental inflammation: role in maternal obesity

Abstract: growth response protein-1 mediates lipotoxicity-associated placental inflammation: role in maternal obesity.

Cited by 75 publications

References 81 publications

Low Adherence to Mediterranean Diet in Portugal: Pregnant Women Nutrition in Portugal and its Repercussions

Low Adherence to Mediterranean Diet in Portugal: Pregnant Women Nutrition in Portugal and its Repercussions

Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1

Longitudinal body composition of children born to mothers with normal weight, overweight, and obesity

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