Implication of DNA methylation during lifestyle mediated weight loss

Abstract

Over the past 50 years, the number of overweight/obese people increased significantly, making obesity a global public health challenge. Apart from rare monogenic forms, obesity is a multifactorial disease, most likely resulting from a concerted interaction of genetic, epigenetic and environmental factors. Although recent studies opened new avenues in elucidating the complex genetics behind obesity, the biological mechanisms contributing to individual's risk to become obese are not yet fully understood. Non-genetic factors such as eating behaviour or physical activity are strong contributing factors for the onset of obesity. These factors may interact with genetic predispositions most likely via epigenetic mechanisms. Epigenome-wide association studies or methylome-wide association studies are measuring DNA methylation at single CpGs across thousands of genes and capture associations to obesity phenotypes such as BMI. However, they only represent a snapshot in the complex biological network and cannot distinguish between causes and consequences. Intervention studies are therefore a suitable method to control for confounding factors and to avoid possible sources of bias. In particular, intervention studies documenting changes in obesity-associated epigenetic markers during lifestyle driven weight loss, make an important contribution to a better understanding of epigenetic reprogramming in obesity. To investigate the impact of lifestyle in obesity state specific DNA methylation, especially concerning the development of new strategies for prevention and individual therapy, we reviewed 19 most recent human intervention studies. In summary, this review highlights the huge potential of targeted interventions to alter disease-associated epigenetic patterns. However, there is an urgent need for further robust and larger studies to identify the specific DNA methylation biomarkers which influence obesity.

Keywords: DNA-methylation; epigenetics; intervention; lifestyle; obesity; overweight; weight loss.

Figure 1

Literature search workflow. Schematic presentation of our literature search on PubMed including mash terms, exclusion criteria and publication numbers. In addition, the top figure shows the distribution of the numbers of publications during the recent years, with a sharp increase of publications matching our mash terms since 2010 but also the most significant increase in the last 3 years. (Created with Biorender.com).

Figure 2

Genome-wide DNA methylation and lifestyle mediated weight loss. Scheme summarizes our results based on genome-wide DNA methylation during the previous five years. The figure indicates a reduced mAge which is associated with an improved lifestyle and weight loss. The upper arrow within the figure represents newly identified genes being associated with a weight loss success whereas the lower arrow shows all at least twice reported genes with changes on the methylome based on lifestyle modifications and weight loss. (Created with Biorender.com).