Early hypermethylation of hepaticIgfbp2results in its reduced expression preceding fatty liver in mice
| العنوان: | Early hypermethylation of hepaticIgfbp2results in its reduced expression preceding fatty liver in mice |
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| المؤلفون: | Markus Jähnert, Wenke Jonas, Andreas Fritsche, Robert W. Schwenk, Hans-Ulrich Häring, A Kammel, Annette Schürmann, Andreas Hoeflich, Sophie Saussenthaler, Laura Stirm, Hans-Georg Joost, Harald Staiger |
| المصدر: | Human molecular genetics, 25(12): 2588–2599 Human Molecular Genetics |
| بيانات النشر: | Oxford University Press (OUP), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Blood Glucose, Male, 0301 basic medicine, medicine.medical_specialty, Carbohydrate metabolism, Biology, Diet, High-Fat, Impaired glucose tolerance, Mice, whole blood, mice, plasma, fatty liver, insulin, methylation, diet, igfbp2 protein, human, respiratory rate, obesity, liver, 03 medical and health sciences, Internal medicine, Genetics, medicine, Animals, Humans, Insulin, Obesity, Molecular Biology, Genetics (clinical), Adiponectin, Leptin, Fatty liver, Articles, General Medicine, Methylation, DNA Methylation, Middle Aged, medicine.disease, Fatty Liver, Insulin-Like Growth Factor Binding Protein 2, 030104 developmental biology, Endocrinology, Adipose Tissue, Gene Expression Regulation, Liver, DNA methylation, Female, Insulin Resistance, Steatosis |
| الوصف: | Obesity and ectopic fat disposition are risk factors for metabolic disease. Recent data indicate that IGFBP2 expression in liver is epigenetically inhibited during hepatic steatosis. The aim of this study was to investigate if epigenetic de-regulation of hepatic Igfbp2 occurs already early in life and is associated with increased risk for diet-induced obesity (DIO) during adolescence. Male C57BL/6J mice received a high-fat diet. After 3 weeks on this diet (age of 6 weeks), DIO-susceptible (responder, Resp) and DIO-resistant (non-responder, nResp) mice were identified by early weight gain. At the age of 6 weeks, Resp mice exhibited elevated blood glucose (p < 0.05), plasma insulin (p < 0.01), HOMA-IR and leptin/adiponectin ratio, whereas liver triglycerides were identical but significantly increased (p < 0.01) in Resp mice at 20 weeks of age. Igfbp2 expression was reduced in young Resp compared with nResp mice (p < 0.01), an effect that correlated with elevated DNA methylation of intronic CpG2605 (p < 0.01). The epigenetic inhibition of Igfbp2 was stable over time and preceded DIO and hepatosteatosis in adult mice. In vitro studies demonstrated that selective methylation of CpG2605 significantly reduced reporter activity by ∼85%, indicating that Igfbp2 expression is modulated by methylation. In human whole blood cells, methylation of IGFBP2 at the homologous CpG site was increased in obese men with impaired glucose tolerance. In conclusion, our data show that increased methylation of hepatic Igfbp2 during infancy predicts the development of fatty liver later in life and is linked to deterioration of glucose metabolism. |
| تدمد: | 1460-2083 0964-6906 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ddf79a2f50c2293c2613063fb9fe9a69 https://doi.org/10.1093/hmg/ddw121 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ddf79a2f50c2293c2613063fb9fe9a69 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602083 09646906 |
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