Nutritional Factors, DNA Methylation, and Risk of Type 2 Diabetes and Obesity: Perspectives and Challenges

Abstract

A healthy diet improves life expectancy and helps to prevent common chronic diseases such as type 2 diabetes (T2D) and obesity. The mechanisms driving these effects are not fully understood, but are likely to involve epigenetics. Epigenetic mechanisms control gene expression, maintaining the DNA sequence, and therefore the full genomic information inherited from our parents, unchanged. An interesting feature of epigenetic changes lies in their dynamic nature and reversibility. Accordingly, they are susceptible to correction through targeted interventions. Here we will review the evidence supporting a role for nutritional factors in mediating metabolic disease risk through DNA methylation changes. Special emphasis will be placed on the potential of using DNA methylation traits as biomarkers to predict risk of obesity and T2D as well as on their response to dietary and pharmacological (epi-drug) interventions.

Molecular basis of ageing in chronic metabolic diseases

“…Accordingly, approaches that are successful in counteracting obesity and ageing, such as exercise and nutritional interventions, exert their health effects by targeting cellular senescence in AT [25,26,52,87]. As epigenetic factors respond adaptively to lifestyle they may be implicated independently of age in the acquisition of a senescent phenotype [51,[88][89][90][91][92][93].…”

“…These changes include DNA methylation, chromatin remodelling, histone modifications, and non-coding RNA transcription [89,[142][143][144]. Although each of these mechanisms is functionally relevant, geroscience research has best characterized the role of DNA methylation dynamics during ageing and their involvement in cellular senescence [142,143].…”

“…Generally, CpG methylation at promoters and enhancers causes gene silencing through chromatin condensation (i.e., heterochromatin). Conversely, a decrease in DNA methylation correlates with heterochromatin de-condensation and gene expression [89].…”

Epigenetic contribution to obesity

“…Reducing caloric intake by adjusting meal size or meal frequency (time-restricted feeding, intermittent fasting) has beneficial effects on health, such as reducing body weight and delaying the onset of chronic diseases like T2D (Di Francesco et al 2018 ; Parrillo et al 2019 ). An elegant study was performed by Milagro et al, evaluating DNA methylation pattern in PBMCs before and after a short-term (8 weeks) caloric restriction.…”

A role of glycation and methylation for SARS-CoV-2 infection in diabetes?

“…These considerations arise also from the knowledge that diabetes has a strict link with DNA methylation of genes involved in islet beta-cell function, as well as in insulin resistance of peripheral tissues such as liver, muscle, and adipose tissue [15] ; moreover the DNA methylation appears as a non-permanent condition, linked also to degree of diabetes control, and a potential target for diabetes control and therapy evaluation [16] , [17] . DNA methylation, besides being considered as a biomarker to predict the risk of obesity and T2D, has been suggested also as a target for dietary and pharmacological treatments [18] . On the other side, glycation processes represent one of the most investigated milestones in pathogenesis, evolution and therapeutic target of diabetes [19] , [20] .…”