Epigenetic mechanisms that underpin metabolic and cardiovascular diseases

An organism's ability to adjust its phenotypic development to the environment is partly determined by epigenetic changes that are established in early life and modulate gene expression during development and maturity. A mismatch between the inducing and the mature environment may result in inappropriate patterns of epigenetic marks and of gene expression that increase the organism's susceptibility to chronic noncommunicable disease. The authors review the relationships between environmental influences during mammalian development, epigenetic changes and metabolic and cardiovascular diseases, and discuss the implications for prevention and treatment. Cellular commitment to a specific lineage is controlled by differential silencing of genes, which in turn depends on epigenetic processes such as DNA methylation and histone modification. During early embryogenesis, the mammalian genome is 'wiped clean' of most epigenetic modifications, which are progressively re-established during embryonic development. Thus, the epigenome of each mature cellular lineage carries the record of its developmental history. The subsequent trajectory and pattern of development are also responsive to environmental influences, and such plasticity is likely to have an epigenetic basis. Epigenetic marks may be transmitted across generations, either directly by persisting through meiosis or indirectly through replication in the next generation of the conditions in which the epigenetic change occurred. Developmental plasticity evolved to match an organism to its environment, and a mismatch between the phenotypic outcome of adaptive plasticity and the current environment increases the risk of metabolic and cardiovascular disease. These considerations point to epigenetic processes as a key mechanism that underpins the developmental origins of chronic noncommunicable disease. Here, we review the evidence that environmental influences during mammalian development lead to stable changes in the epigenome that alter the individual's susceptibility to chronic metabolic and cardiovascular disease, and discuss the clinical implications. Key Points Developmental plasticity enables an organism to respond to environmental cues and adjust its phenotypic development to match its environment Developmental plasticity is effected, at least in part, by epigenetic changes that are established in early life and modulate gene expression during development and maturity In mammals, the window during which the ep