Weight loss surgery also alters the epigenome
Gastric bypass surgery can drastically reduce the body weight of obese individuals. For reasons that are not entirely clear, the surgery also leads to early remission of type 2 diabetes in the vast majority of patients. In a new article in Cell Reports, researchers from Karolinska Institutet and University of Copenhagen, Denmark now report the discovery of gene-expression alterations in individuals who underwent the surgery compared with obese individuals who did not.
"We provide evidence that in severely obese people, the levels of specific genes that control how fat is burned and stored in the body are changed to reflect poor metabolic health," says senior author Professor Juleen Zierath, of Karolinska Institutet. "After surgery, the levels of these genes are restored to a healthy state, which mirrors weight loss and coincides with overall improvement in metabolism."
When the investigators probed deeper, they found that weight loss after surgery causes changes in DNA modifications that control gene expression in response to the environment. Specifically, changes in methylation, or chemical markings, on two genes that control glucose and fat metabolism (called PGC-1alpha and PDK4) correlate with obesity but are reversed after surgery-induced weight loss. The findings suggest that the environment – in this case food intake or weight loss – can affect gene expression through this mechanism.
According to the researchers, the findings may be useful for the design of new drugs that mimic this weight-loss-associated control of gene regulation.
The study was funded by the European Research Council, the Swedish research Council, the European Foundation for the Study of Diabetes, the European Molecular Biology Organization (EMBO), the Karolinska Institutet Strategic Research Programme in Diabetes, amongst others. A major part of this press release has been originally been published by the Cell Press.
Weight loss after gastric bypass surgery in human obesity remodels promoter methylation.
Cell Rep 2013 Apr;3(4):1020-7