In recent decades, the increasing prevalence of obesity has become a major public health problem worldwide. An estimated 200 million adults in the U.S. (or a staggering 68% of the adult population) are categorized as overweight or obese.
 
Obesity has become a significant contributor to rising healthcare costs in the country (total annual healthcare costs for treating obese adults now amount to nearly $150 billion). The condition is a leading cause of type 2 diabetes, disability, heart disease, morbidity, and mortality, resulting in nearly 112,000 deaths in the U.S. annually.
 
Epigenetics
Obesity is a multifactorial disorder where lifestyle and environmental factors (such as dietary habits, sedentary behavior and other environmental exposures) and genetics have a role. More specifically, in the last decade there has been an increasing interest in the role of epigenetics in the development of this complex condition.
 
The term epigenetics refers to modifications in gene expression that are controlled by heritable, but potentially reversible, changes in DNA methylation and/or chromatin structure which are not accompanied by any change in DNA sequences. Epigenetic mechanisms constitute an essential mode of gene regulation and act as an interface between environmental exposures, cellular response and pathological processes, thereby determining whether or not the gene is active in a given cell at a given time.
 
DNA methylation is of major importance in defining cellular identity and differentiation of adipocytes. The study of DNA methylation profiles in different adipose tissue depots under different metabolic conditions could provide information about how epigenetic regulation of adipose tissue is involved in the development of obesity and associated comorbidities, and how this could potentially be manipulated.
 
Today we know that diet is one of the most studied environmental factors in epigenetic change. There is now mounting evidence supporting the idea that nutrients may modify the pattern of DNA methylation.
 
DNA Methylation
The most compelling evidence of involvement of nutrients in DNA methylation is by folate because of its participation in one-carbon metabolism. One-carbon metabolism is a network of interrelated biochemical reactions that involves the transfer of one-carbon groups from one biological compound to another (methylation) and is essential for sustaining the life of cells.
 
Questions are now being asked about the possible role of folate and other nutrients involved in the one-carbon metabolism in the manipulation of methylation status and obesity.
 
In animal studies, the modification of DNA methylation by methyl donor supplementation has been shown to prevent transgenerational amplification of obesity in the well worked Agouti mouse model of genetic predisposition to obesity. In a recent scientific work of Naifeng Zhang (Animal Nutrition 2015) the epigenetic modulation of DNA methylation by nutrition and its mechanisms in animals has been evaluated. The author describes that there are three possible ways nutrition influences patterns of DNA methylation: first, provision of substrates being necessary for proper DNA methylation; second, provision of cofactors modulating the enzymatic activity of enzyme involved; third, changing activity of the enzymes regulating the one-carbon cycle. Importantly, all three mechanisms are mutually compatible and may operate together in time.
 
In this light, the universal methyl-donor for DNA S-Adenosylmethionine (SAMe) as well as active folate entering at different sites in the one-carbon metabolism may contribute to the right methylation pathway of the body.
 
Nevertheless, as reported by the recent review published by the International Journal of Obesity, significant progress has been made in the field of epigenetics and obesity, and there is still much to be learned before we fully understand the role of the epigenome in development of this complex disease.