Andrew Feinberg, M.D.
Johns Hopkins University
NIEHS Grant DP1ES022579
Research supported in part by NIEHS found a surprising similarity between obesity-induced epigenetic marks in mice and humans. These findings might provide new routes to prevent and study obesity as well as insight into how the environment might bring about epigenetic changes that can lead to obesity-related diseases such as type 2 diabetes.
Epigenetic marks are chemical modifications, such as the addition of a methyl group, that change how DNA is expressed without changing the genetic code. The researchers analyzed more than 7 million sites in the DNA of fat cells in lean and obese mice and found clear differences in methylation patterns. They also looked at how DNA methylation changes in people before and after gastric bypass surgery. Of the 625 regions of DNA with methylation patterns associated with obesity in the mice, 249 regions showed significant conserved methylation changes associated with obesity in people.
The investigators used genetic association data from a large type 2 diabetes genome-wide association study (GWAS) to link their findings with disease. This revealed that some of the obesity-associated methylation patterns affected genes known to raise diabetes risk while others affected genes that had not been conclusively linked to the disease but that did have roles in metabolism. It also identified some DNA regions that might be susceptible to environmental factors that influence methylation.
Citation: Citation: Multhaup ML, Seldin MM, Jaffe AE, Lei X, Kirchner H, Mondal P, Li Y, Rodriguez V, Drong A, Hussain M, Lindgren C, McCarthy M, Näslund E, Zierath JR, Wong GW, Feinberg AP. 2015. Mouse-human experimental epigenetic analysis unmasks dietary targets and genetic liability for diabetic phenotypes. Cell Metab. 21(1):138-149.