Epigenome modifiers and metabolic rewiring: New frontiers in therapeutics

In the last decade numerous publications highlighted the connection between metabolism and epigenetics in different physiological and pathological conditions. The availability of metabolites for cells represents indeed a crucial factor, which is able to condition cell fate and development, differentiation and proliferation partially trough epigenetic control. This tight link provides novel therapeutic possibilities to treat many pathological conditions induced by epigenetic alterations, by manipulating metabolic pathways producing metabolites that work also as epigenetic modifiers. This review will explore specifically the relevance of epigenetics and metabolism in the onset of metabolic disorders and cancer, highlighting potential epigenetic-based pharmacological approaches for the treatment of these disorders trough a rewiring of cellular metabolism. We will also report recent studies on stem cells, demonstrating how epigenetic setting is influenced by metabolism and how these processes affect cell pluripotency and differentiation capacity. These findings suggest a big pharmacological potential, as the modulation of epigenetics and metabolism in stem cells may represent a new tool for regenerative medicine, offering a plethora of novel possibilities for the treatment of severe pathological conditions. (C) 2018 Elsevier Inc. All rights reserved.