Academic Journal
Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation
| العنوان: | Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation |
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| المؤلفون: | Puppala, Sobha, Li, Cun, Glenn, Jeremy P., Saxena, Romil, Gawrieh, Samer, Quinn, Amy, Palarczyk, Jennifer, Dick, Edward J., Nathanielsz, Peter W., Cox, Laura A. |
| المساهمون: | National Institutes of Health |
| المصدر: | The Journal of Physiology ; volume 596, issue 23, page 5823-5837 ; ISSN 0022-3751 1469-7793 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2018 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Key points Maternal obesity (MO) and exposure to a high‐fat, high‐simple‐carbohydrate diet during pregnancy predisposes offspring to obesity, metabolic and cardiovascular disorders in later life. Underlying molecular pathways and potential epigenetic factors that are dysregulated in MO were identified using unbiased transcriptomic methods. There was increased lipid accumulation and severe steatosis in the MO baboon fetal liver suggesting that these offspring are on an early trajectory of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis. Abstract Maternal obesity (MO) increases offspring cardiometabolic disease risk. Altered fetal liver development in response to the challenge of MO has metabolic consequences underlying adverse offspring life‐course health outcomes. Little is known about the molecular pathways and potential epigenetic changes regulating primate fetal liver responses to MO. We hypothesized that MO would induce fetal baboon liver epigenetic changes resulting in dysregulation of key metabolic pathways that impact lipid metabolism. MO was induced prior to pregnancy by a high‐fat, high‐fructose diet. Unbiased gene and microRNA (small RNA Seq) abundance analyses were performed on fetal baboon livers at 0.9 gestation and subjected to pathway analyses to identify fetal liver molecular responses to MO. Fetal baboon liver lipid and glycogen content were quantified by the Computer Assisted Stereology Toolbox. In response to MO, fetal livers revealed dysregulation of TCA cycle, proteasome, oxidative phosphorylation, glycolysis and Wnt/β‐catenin signalling pathways together with marked lipid accumulation supporting our hypothesis that multiple pathway dysregulation detrimentally impacts lipid management. This is the first study of MO programming of the non‐human primate fetal liver using unbiased transcriptome analysis to detect changes in hepatic gene expression levels and identify potential microRNA epigenetic regulators of metabolic disruption. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1113/jp275422 |
| DOI: | 10.1113/JP275422 |
| الاتاحة: | http://dx.doi.org/10.1113/jp275422 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1113%2FJP275422 https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/JP275422 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.CD823AEC |
| قاعدة البيانات: | BASE |
| DOI: | 10.1113/jp275422 |
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