Epigenetic mechanisms that underpin metabolic and cardiovascular diseases

Abstract

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.

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

“…Indeed, a persistent change in early gene transcription may alter behavior and organ functions and be involved in the susceptibility and the age of onset of different metabolic disorders due to the in utero insult (Heerwagen et al, 2010). This is in relation with the concept of developmental plasticity, that enables an organism to adjust its phenotype to the environmental cues (Gluckman et al, 2009). A mismatch between the phenotypic outcome of adaptive plasticity and the current environment increases susceptibility to metabolic diseases and is the basis of the Developmental Origins of Health and Disease (DOHaD) hypothesis.…”

Effect of intrauterine growth retardation on liver and long-term metabolic risk

“…19,20 The epigenetic control of gene expression is based on modulation of chromatin structure and accessibility to transcription factors. This type of control is achieved by multiple mechanisms such as methylation-demethylation of cytidine-guanosine (CpG) sequences in the promoter regions, acetylation-deacetylation of lysine residues of core histones in the nucleosome and the presence of microRNA molecules that bind to complementary sequences in the 3 0 end of mRNA and reduce the rate of protein synthesis.…”

In vitro antitumor activity of chemical constituents of EtOAc extract from Artemisa gmelinii

“…Diphenylethene is a group of natural organic compounds with a C 6 -C 2 -C 6 unit in the parent nucleus, which have a variety of biological activities, such as anti-tumor, antihypertensive, ester, antiplatelet aggregation, antibacterial and so on. For example, resveratrol is a widely known natural product, which exhibited significant pharmacological activities [23][24][25][26] and considered a plant antitoxin. The structure of compound 5 can be regarded as the oxidized and cyclization of the vinyl group (C 2 ) in diphenylethene.…”

“…The EtOAc extract (180.0 g) was isolated by column chromatography on silica gel and gradiently eluted with CHCl 3 -MeOH (50:1 to 10:1) to give 3 fractions (Fr. C [1][2][3] …”

“…Tumor is the most common and frequently occurring diseases, of which malignant carcinoma is one of the most serious diseases that endanger human health [1][2][3]. It is estimated that annual tumor cases will rise from 14 million in 2012 to 22 million within the next two decades [4][5][6].…”