Maternal metformin treatment decreases fetal inflammation in a rat model of obesity and metabolic syndrome

Desai, Neeraj; Roman, Amanda; Rochelson, Burton; Gupta, Madhu; Xue, Xiangying; Chatterjee, Prodyot K.; Tam, Hima Tam; Metz, Christine N.

doi:10.1016/j.ajog.2013.05.001

Cited by 47 publications

(43 citation statements)

References 51 publications

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“…Preconception care with insulin treatment and blood glucose-reducing agents decreases the incidence of birth defects in diabetic or obese pregnancies 41, 42 ; however, even women with diabetes under modern preconception care have a higher chance of having babies with birth defects, compared with nondiabetic women.…”

Section: Resultsmentioning

confidence: 99%

Curcumin ameliorates high glucose-induced neural tube defects by suppressing cellular stress and apoptosis

Wang

Reece

et al. 2015

American Journal of Obstetrics and Gynecology

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Objectives Curcumin is a naturally occurring polyphenol present in the roots of the Curcuma longa plant (turmeric), which possesses antioxidant, anti-tumorigenic and anti-inflammatory properties. Here, we test whether curcumin treatment reduces high glucose-induced neural tube defects (NTDs), and if this occurs via blocking cellular stress and caspase activation. Study Design Embryonic day 8.5 mouse embryos were collected for use in whole embryo culture under normal glucose (100 mg/dl glucose) or high glucose (300 mg/dl glucose) conditions, with or without curcumin treatment. After 24 h in culture, protein levels of oxidative stress makers, nitrosative stress makers, endoplasmic reticulum (ER) stress makers, cleaved caspase 3 and 8 and the level of lipid peroxides (LPO) were determined in the embryos. After 36 h in culture, embryos were examined for evidence of NTD formation. Results Although 10 μM curcumin did not significantly reduce the rate of NTDs caused by high glucose, 20 μM curcumin significantly ameliorated high glucose-induced NTD formation. Curcumin suppressed oxidative stress in embryos cultured under high glucose conditions. Treatment reduced the levels of the lipid peroxidation marker, 4-hydroxynonenal(4-HNE), nitrotyrosine-modified protein, and LPO. Curcumin also blocked ER stress by inhibiting phosphorylated protein kinase ribonucleic acid (RNA)-like ER kinase (p-PERK), phosphorylated inositol-requiring protein-1α (p-IRE1α), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), binding immunoglobulin protein (BiP) and x-box binding protein 1 (XBP1) mRNA splicing. Additionally, curcumin abolished caspase 3 and caspase 8 cleavage in embryos cultured under high glucose conditions. Conclusions Curcumin reduces high glucose-induced NTD formation by blocking cellular stress and caspase activation, suggesting that curcumin supplements could reduce the negative effects of diabetes on the embryo. Further investigation will be needed to determine if the experimental findings can translate into clinical settings.

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Section: Resultsmentioning

confidence: 99%

Curcumin ameliorates high glucose-induced neural tube defects by suppressing cellular stress and apoptosis

Wang

Reece

et al. 2015

American Journal of Obstetrics and Gynecology

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“…Notably, in humans, obese mothers have increased IL-6 in plasma and breast milk and increased IL-6 gene expression in placental macrophages [54-56]. In rodents, increased fetal IL-6 levels from high fat/sugar-fed dams are also observed [57]. Prenatal exposure to IL-6, either through maternal immune activation (MIA) or cytokine injection, is sufficient to cause aberrant ASD-like behaviors and altered brain transcriptomes in offspring [58,59].…”

Section: Discussionmentioning

confidence: 99%

“…In human children and adults, obesity is associated with increased anxiety and associations are sometimes stronger in females [16,57]. Examination of non-human primate offspring from maternally obese mothers also revealed a female bias for elevated anxiety [19].…”

Section: Discussionmentioning

confidence: 99%

Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring

Kang

Kurti

Fair

et al. 2014

J Neuroinflammation

134

101

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Obesity induces a low-grade inflammatory state and has been associated with behavioral and cognitive alterations. Importantly, maternal environmental insults can adversely impact subsequent offspring behavior and have been linked with neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (AHDH). It is unknown if maternal obesity significantly alters offspring sociability, a key ASD feature, and if altering maternal diet will provide an efficacious intervention paradigm for behavioral deficits. Here we investigated the impact of maternal high fat diet (HFD) and maternal dietary intervention during lactation on offspring behavior and brain inflammation in mice. We found that maternal HFD increased anxiety and decreased sociability in female offspring. Additionally, female offspring from HFD-fed dams also exhibited increased brain IL-1β and TNFα and microglial activation. Importantly, maternal dietary intervention during lactation was sufficient to alleviate social deficits and brain inflammation. Maternal obesity during gestation alone was sufficient to increase hyperactivity in male offspring, a phenotype that was not ameliorated by dietary intervention. These data suggest that maternal HFD acts as a prenatal/perinatal insult that significantly impacts offspring behavior and inflammation and that dietary intervention during lactation may be an easily translatable, efficacious intervention to offset some of these manifestations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0156-9) contains supplementary material, which is available to authorized users.

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“…In animal models, pharmaceutical treatments that improve maternal metabolic and inflammatory status have beneficial effects on mother and offspring, but long-term safety and efficacy have not been verified [9,10]. Therefore, nutritional-based strategies pose promising avenues for the intervention of programmed adult offspring disease.…”

Section: Introductionmentioning

confidence: 97%

Maternal supplementation with conjugated linoleic acid in the setting of diet-induced obesity normalises the inflammatory phenotype in mothers and reverses metabolic dysfunction and impaired insulin sensitivity in offspring

Segovia

Vickers

Zhang

et al. 2015

The Journal of Nutritional Biochemistry

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Maternal metformin treatment decreases fetal inflammation in a rat model of obesity and metabolic syndrome

Cited by 47 publications

References 51 publications

Curcumin ameliorates high glucose-induced neural tube defects by suppressing cellular stress and apoptosis

Curcumin ameliorates high glucose-induced neural tube defects by suppressing cellular stress and apoptosis

Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring

Maternal supplementation with conjugated linoleic acid in the setting of diet-induced obesity normalises the inflammatory phenotype in mothers and reverses metabolic dysfunction and impaired insulin sensitivity in offspring

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