Lack of folate linked to epigenetic changes in diabetes

UEF Bulletin 2016

A recent study revealed a new epigenetic link between diet and type 2 diabetes. Reduced folate levels were found to be associated with altered DNA methylation in the liver of people with diabetes.

Folate levels in the body reflect the intake of foods rich in folate, such as dark green leafy vegetables, legumes and whole-grain products, including rye bread. “On the basis of our results, it can be assumed that an insufficient folate intake may lead to epigenetic changes in the liver, which in turn may contribute to the pathogenesis of type 2 diabetes,” says Jussi Pihlajamäki, Professor of Clinical Nutrition.

Many genes are known to increase the risk of type 2 diabetes, but it has been shown that even those genetically predisposed can reduce their risk by changing their lifestyles and eating healthy. Epigenetic mechanisms may explain how lifestyle can affect the genetic risk.

Epigenetic mechanisms can cause stable, permanent or even heritable changes in gene activity without changing the gene itself. One such mechanism is DNA methylation, the addition of a methyl group to DNA, usually resulting in reduced gene expression.

In healthy people, the liver plays an important role in maintaining glucose homeostasis, but in type 2 diabetes, it fails to do so. Whether some of the pathology could be attributed to altered DNA methylation has so far remained unknown.

Together with researchers from Lund University, Pihlajamäki’s research group investigated the genome-wide DNA methylation pattern in the liver of 35 subjects with type 2 diabetes and 60 non-diabetic controls. They also compared the methylation differences to gene expression and erythrocyte folate levels.

Significant differences between diabetics and controls were found at 251 methylation sites. Some 236 of these sites displayed decreased DNA methylation in people with diabetes, including sites in genes previously linked to type 2 diabetes. Twenty-nine genes displayed both differential DNA methylation and gene expression in the liver of people with diabetes. Decreased DNA methylation was also associated with reduced folate levels.

Folate serves as a methyl donor in the methylation cycle, which could explain why the lack of folate could reduce DNA methylation.

In Finland, insufficient folate intake is common, especially among women. However, Pihlajamäki would recommend getting your daily folate from food rather than from a supplement. "Folate is just one marker of a healthy diet. Our results highlight the downsides of the lack of folate, but not any benefits of over-supplementation."

Text: Ulla Kaltiala Photo: Raija Törrönen