<i>PPARG</i> Hypermethylation as the First Epigenetic Modification in Newly Onset Insulin Resistance in Human Adipocytes
Insulin acts by binding with a specific receptor called an insulin receptor (INSR), ending up with glucose transporter activation and glucose uptake. Insulin resistance (IR) is a state when the physiological amount of insulin is not sufficient to evoke proper action, i.e., glucose uptake. Epigenetic...
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MDPI AG
2021-06-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/6/889 |
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| author | Małgorzata Małodobra-Mazur Aneta Cierzniak Krzysztof Kaliszewski Tadeusz Dobosz |
| author_facet | Małgorzata Małodobra-Mazur Aneta Cierzniak Krzysztof Kaliszewski Tadeusz Dobosz |
| author_sort | Małgorzata Małodobra-Mazur |
| collection | DOAJ |
| description | Insulin acts by binding with a specific receptor called an insulin receptor (INSR), ending up with glucose transporter activation and glucose uptake. Insulin resistance (IR) is a state when the physiological amount of insulin is not sufficient to evoke proper action, i.e., glucose uptake. Epigenetic modifications associated with obesity and IR are some of the main mechanisms leading to IR pathogenesis. The mesenchymal stem cells of adipose tissue (subcutaneous (SAT) and visceral (VAT)) were collected during abdominal surgery. IR was induced ex vivo by palmitic acid. DNA methylation was determined at a global and site-specific level. We found higher global DNA methylation in IR adipocytes after 72 h following IR induction. Furthermore, numerous genes regulating insulin action (<i>PPARG</i>, <i>SLC2A4</i>, <i>ADIPOQ</i>) were hypermethylated in IR adipocytes; the earliest changes in site-specific DNA methylation have been detected for <i>PPARG</i>. Epigenetic changes appear to be mediated through DNMT1. DNA methylation is an important component of IR pathogenesis; the <i>PPARG</i> and its epigenetic modification appear to be the very first epigenetic modification in newly onset IR and are probably of the greatest importance. |
| first_indexed | 2024-03-10T10:35:15Z |
| format | Article |
| id | doaj.art-807b799a723145dda4e1a8fe4159ab43 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T10:35:15Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-807b799a723145dda4e1a8fe4159ab432023-11-21T23:21:10ZengMDPI AGGenes2073-44252021-06-0112688910.3390/genes12060889<i>PPARG</i> Hypermethylation as the First Epigenetic Modification in Newly Onset Insulin Resistance in Human AdipocytesMałgorzata Małodobra-Mazur0Aneta Cierzniak1Krzysztof Kaliszewski2Tadeusz Dobosz3Department of Forensic Medicine, Wroclaw Medical University, Sklodowskiej-Curie 52, 50-369 Wroclaw, PolandDepartment of Forensic Medicine, Wroclaw Medical University, Sklodowskiej-Curie 52, 50-369 Wroclaw, PolandDepartment of General, Minimally Invasive and Endocrine Surgery, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandDepartment of Forensic Medicine, Wroclaw Medical University, Sklodowskiej-Curie 52, 50-369 Wroclaw, PolandInsulin acts by binding with a specific receptor called an insulin receptor (INSR), ending up with glucose transporter activation and glucose uptake. Insulin resistance (IR) is a state when the physiological amount of insulin is not sufficient to evoke proper action, i.e., glucose uptake. Epigenetic modifications associated with obesity and IR are some of the main mechanisms leading to IR pathogenesis. The mesenchymal stem cells of adipose tissue (subcutaneous (SAT) and visceral (VAT)) were collected during abdominal surgery. IR was induced ex vivo by palmitic acid. DNA methylation was determined at a global and site-specific level. We found higher global DNA methylation in IR adipocytes after 72 h following IR induction. Furthermore, numerous genes regulating insulin action (<i>PPARG</i>, <i>SLC2A4</i>, <i>ADIPOQ</i>) were hypermethylated in IR adipocytes; the earliest changes in site-specific DNA methylation have been detected for <i>PPARG</i>. Epigenetic changes appear to be mediated through DNMT1. DNA methylation is an important component of IR pathogenesis; the <i>PPARG</i> and its epigenetic modification appear to be the very first epigenetic modification in newly onset IR and are probably of the greatest importance.https://www.mdpi.com/2073-4425/12/6/889insulin resistance<i>PPARG</i>DNA methylation<i>DNMT1</i>SATVAT |
| spellingShingle | Małgorzata Małodobra-Mazur Aneta Cierzniak Krzysztof Kaliszewski Tadeusz Dobosz <i>PPARG</i> Hypermethylation as the First Epigenetic Modification in Newly Onset Insulin Resistance in Human Adipocytes Genes insulin resistance <i>PPARG</i> DNA methylation <i>DNMT1</i> SAT VAT |
| title | <i>PPARG</i> Hypermethylation as the First Epigenetic Modification in Newly Onset Insulin Resistance in Human Adipocytes |
| title_full | <i>PPARG</i> Hypermethylation as the First Epigenetic Modification in Newly Onset Insulin Resistance in Human Adipocytes |
| title_fullStr | <i>PPARG</i> Hypermethylation as the First Epigenetic Modification in Newly Onset Insulin Resistance in Human Adipocytes |
| title_full_unstemmed | <i>PPARG</i> Hypermethylation as the First Epigenetic Modification in Newly Onset Insulin Resistance in Human Adipocytes |
| title_short | <i>PPARG</i> Hypermethylation as the First Epigenetic Modification in Newly Onset Insulin Resistance in Human Adipocytes |
| title_sort | i pparg i hypermethylation as the first epigenetic modification in newly onset insulin resistance in human adipocytes |
| topic | insulin resistance <i>PPARG</i> DNA methylation <i>DNMT1</i> SAT VAT |
| url | https://www.mdpi.com/2073-4425/12/6/889 |
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