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High Dietary Fat Intake Affects DNA Methylation/Hydroxymethylation in Mouse Heart: Epigenetic Hints for Obesity‐Related Cardiac Dysfunction
Author(s) -
Ciccarone Fabio,
Castelli Serena,
Ioannilli Laura,
Ciriolo Maria Rosa
Publication year - 2019
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201800970
Subject(s) - epigenetics , dna methylation , biology , downregulation and upregulation , obesity , medicine , endocrinology , methylation , oxidative stress , gene , gene expression , genetics
Scope Epigenetic aberrations caused by environmental factors and lifestyle choices have been associated with the development of a number of pathologies, including cardiovascular disorders. However, whether obesity‐related heart dysfunction can occur via epigenetic mechanisms is largely undisclosed. The manifested role of DNA hydroxymethylation in heart pathophysiology prompts an investigation of its levels/machinery in heart of mice fed with high‐fat diet (HFD) and its possible relation with genes linked to obesity‐associated cardiac remodeling. Methods and results Alterations in levels of DNA methylation/hydroxymethylation modifications and in expression of Tet family of DNA hydroxylases are observed in hearts of mice treated with HFD for 8 and 16 weeks. Decreased levels of the Tet co‐substrate α‐ketoglutarate are also observed and associate with mitochondrial mass reduction and augmented oxidative stress. Finally, expression markers of cardiac remodeling are monitored by RT‐qPCR analysis and associate with DNA hydroxymethylation signature by DNA immunoprecipitation and correlation analyses. Conclusion Global changes of DNA hydroxymethylation in hearts of HFD‐fed mice are associated with upregulation of the dioxygenase Tet3 and decreased content of α‐ketoglutarate. A relation between Tet genes and markers of cardiac hypertrophic response is observed and, if further validated, it will provide insights concerning epigenetics and obesity‐related cardiac complications.