Aberrant DNA Methylation Mediates the Transgenerational Risk of Metabolic and Chronic Disease Due to Maternal Obesity and Overnutrition

Abstract

Maternal obesity is a rapidly evolving universal epidemic leading to acute and long-term medical and obstetric health issues, including increased maternal risks of gestational diabetes, hypertension and pre-eclampsia, and the future risks for offspring's predisposition to metabolic diseases. Epigenetic modification, in particular DNA methylation, represents a mechanism whereby environmental effects impact on the phenotypic expression of human disease. Maternal obesity or overnutrition contributes to the alterations in DNA methylation during early life which, through fetal programming, can predispose the offspring to many metabolic and chronic diseases, such as non-alcoholic fatty liver disease, obesity, diabetes, and chronic kidney disease. This review aims to summarize findings from human and animal studies, which support the role of maternal obesity in fetal programing and the potential benefit of altering DNA methylation to limit maternal obesity related disease in the offspring.

Keywords: DNA methylation; maternal obesity; metabolic diseases; offspring; overnutrition.

Figure 1

The dynamic and reversible processes of DNA methylation. The whole epigenetic progression of 5mC contains three aspects: de novo methylation, methylation maintenance, and demethylation. DNMT3A and DNMT3B were reported to be involved in de novo methylation, while DNMT1 was found to participate in the maintenance of DNA methylation. Besides, the process of demethylation can be divided into two parts: passive demethylation and active demethylation. Passive DNA demethylation is attributed to the absence of DNMTs, while active demethylation is due to the involvement of TET or TDG enzymes and BER repair pathway. Abbreviation: DNA methyltransferase: DNMT; Ten eleven translocation: TET; Thymine DNA glycosylase: TDG; Base excision repair: BER; Fifth position of cytosine: 5mC; 5-hydroxymethylcytosine: 5hmC; 5-formylcytosine: 5fC; 5-carboxylcytosine: 5caC.