Abnormal lipid metabolism in metabolic syndrome: an epigenetic perspective

Open access

Abstract

Metabolic syndrome is a complex pathology including central obesity, impaired glucose tolerance/diabetes, an atherogenic dyslipidemia and a prothrombotic state.

A new perspective on understanding the mechanisms underlying metabolic syndrome is provided by the epigenetic changes (mainly DNA methylation and histone covalent modifications), which influence gene expression without changing of the DNA sequence.

DNA methylation (mainly in carnitine palmitoyltransferase 1A gene) and histone modifications were shown to be associated with VLDL and LDL phenotypes, with hyperglycemia and reduced level of HDL cholesterol, with hypertriglyceridemic waist phenotype and with progression of atherosclerotic occlusion in peripheral arteries. The epigenetic changes can occur in the prenatal period, throughout the life span, and can be transmitted to the offspring. Both poor maternal nutrition and maternal obesity, diabetes and overfeeding can result in epigenetic alterations that amplify the risk of metabolic syndrome for the offspring.

Throughout life span, environmental factors, such as nutrition and exercise can induce epigenetic changes influencing the evolution of the metabolic syndrome (through adipocyte metabolism and insulin signaling pathway). The epigenetic modifications are not completely erased during gametogenesis and embryogensis, resulting in a transgenerational transmission of an epigenetic state up to the fifth generation.

Epigenetic mechanisms are an interface between environmental stimuli and resulting phenotype by inducing a certain transcriptional state, which may be also transmitted to the next generation(s) and which may predispose to an increased risk for developing metabolic syndrome in the context of a mismatched environment.

Elucidating epigenetic modulation might provide additional information about risk evaluation and more targeted therapeutical intervention.

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Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

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