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.
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.
Authors: Robertina Giacconi; Marco Malavolta; Alexander Bürkle; María Moreno-Villanueva; Claudio Franceschi; Miriam Capri; P Eline Slagboom; Eugène H J M Jansen; Martijn E T Dollé; Tilman Grune; Daniela Weber; Antti Hervonen; Wolfgang Stuetz; Nicolle Breusing; Fabio Ciccarone; Michele Zampieri; Valentina Aversano; Paola Caiafa; Laura Formentini; Francesco Piacenza; Elisa Pierpaoli; Andrea Basso; Mauro Provinciali; Maurizio Cardelli Journal: Nutrients Date: 2019-12-06 Impact factor: 5.717
Authors: Mohsen Afarideh; Roman Thaler; Farzaneh Khani; Hui Tang; Kyra L Jordan; Sabena M Conley; Ishran M Saadiq; Yasin Obeidat; Aditya S Pawar; Alfonso Eirin; Xiang-Yang Zhu; Amir Lerman; Andre J van Wijnen; Lilach O Lerman Journal: Epigenetics Date: 2020-09-20 Impact factor: 4.528