1. Dietary fatty acids modulate adipocyte TNFa production via regulation of its DNA promoter methylation levels.
- Author
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García-Escobar E, Monastero R, García-Serrano S, Gómez-Zumaquero JM, Lago-Sampedro A, Rubio-Martín E, Colomo N, Rodríguez-Pacheco F, Soriguer F, and Rojo-Martínez G
- Subjects
- 3T3-L1 Cells, Adipocytes, White drug effects, Adipocytes, White metabolism, Animals, Coconut Oil administration & dosage, DNA Modification Methylases antagonists & inhibitors, DNA Modification Methylases metabolism, Enzyme Inhibitors pharmacology, Fatty Acids, Unsaturated metabolism, Intra-Abdominal Fat drug effects, Linoleic Acids metabolism, Male, Mice, Oleic Acid metabolism, Olive Oil administration & dosage, Palmitic Acid metabolism, Random Allocation, Rats, Sprague-Dawley, Sunflower Oil administration & dosage, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha genetics, DNA Methylation drug effects, Epigenesis, Genetic drug effects, Fatty Acids, Unsaturated administration & dosage, Gene Expression Regulation drug effects, Intra-Abdominal Fat metabolism, Promoter Regions, Genetic drug effects, Tumor Necrosis Factor-alpha metabolism
- Abstract
The factors regulating TNF alpha (TNFa) levels could be considered therapeutic targets against metabolic syndrome development. DNA methylation is a potent regulator of gene expression and may be associated with protein levels. In this study we investigate whether the effect of dietary fatty acids on TNFa released from adipocytes might be associated with modifications of the TNFa promoter DNA methylation status. A group of rats was assigned to three diets with a different composition of saturated, monounsaturated and polyunsaturated fatty acids. Samples of visceral adipose tissues were taken for adipocyte isolation, in which released TNFa levels were measured, and for methylation and expression studies. In addition, 3 T3-L1 cells were treated with palmitic, oleic and linoleic acids, with and without 5-Azacitydine (5-AZA). After treatments, cells and supernatants were included in the same analyses as rat samples. TNFa promoter methylation levels, gene expression and secretion were different according to the diets and fatty acid treatments associated with them. Cells treated with 5-AZA displayed higher TNFa levels than in the absence of 5-AZA, without differences between fatty acids. According to our results, dietary fatty acid regulation of adipocyte TNFa levels may be mediated by epigenetic modifications of the TNFa promoter DNA methylation levels., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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