High Dietary Fat Intake Affects DNA Methylation/Hydroxymethylation in Mouse Heart: Epigenetic Hints for Obesity-Related Cardiac Dysfunction

Fabio Ciccarone, Serena Castelli, Laura Ioannilli, Maria Rosa Ciriolo

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)e1800970
JournalMolecular Nutrition and Food Research
Issue number4
Publication statusPublished - Feb 2019


  • Animals
  • Cardiomegaly/genetics
  • Cytoskeletal Proteins
  • DNA Methylation/drug effects
  • DNA-Binding Proteins/genetics
  • Diet, High-Fat
  • Dietary Fats/adverse effects
  • Enzymes/metabolism
  • Epigenesis, Genetic/drug effects
  • Gene Expression Regulation/drug effects
  • Heart/drug effects
  • LIM Domain Proteins/genetics
  • Male
  • Mice, Inbred C57BL
  • Mitochondria, Heart/drug effects
  • Nuclear Proteins/genetics
  • Obesity/genetics
  • Protein Carbonylation/drug effects


Dive into the research topics of 'High Dietary Fat Intake Affects DNA Methylation/Hydroxymethylation in Mouse Heart: Epigenetic Hints for Obesity-Related Cardiac Dysfunction'. Together they form a unique fingerprint.

Cite this