Metaboloepigenetics in cancer, immunity and cardiovascular disease.

The influence of cellular metabolism on epigenetic pathways are well documented but misunderstood. Scientists have long known of the metabolic impact on epigenetic determinants. More often than not, that title role for DNA methylation was portrayed by the metabolite SAM or S-adenosylmethionine. Technically speaking there are many other metabolites that drive epigenetic processes that instruct seemingly distant - yet highly connect pathways - and none more so than our understanding of the cancer epigenome. Recent studies have shown that available energy link the extracellular environment to influence cellular responses. This focused review examines the recent interest in epigenomics and casts cancer, metabolism and immunity in unfamiliar roles - cooperating. There are not only language lessons from cancer research, we have come round to appreciate that reaching into areas previously thought of as too distinct are also object lessons in understanding health and disease. The Warburg effect is one such signature of how glycolysis influences metabolic shift during oncogenesis. That shift in metabolism - now recognised as central to proliferation in cancer biology - influence core enzymes that not only control gene expression but are also central to replication, condensation and the repair of nucleic acid. These nuclear processes rely on metabolism and with glucose at center stage the role of respiration and oxidative metabolism are now synonymous with the mitochondria as the powerhouses of metaboloepigenetics. The emerging evidence for metaboloepigenetics in trained innate immunity has revealed recognisable signalling pathways with antecedent extracellular stimulation. With due consideration to immunometabolism we discuss the striking signalling similarities influencing these core pathways. The immunometabolic-epigenetic axis in cardiovascular disease has deeply etched connections with inflammation and we examine the chromatin template as a carrier of epigenetic indices that determine the expression of genes influencing atherosclerosis and vascular complications of diabetes.