Study finds epigenetic signature for obesity susceptibility in human twins

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Susceptibility to weight gain may be written into the molecular mechanisms of human cells, a Washington State University study suggests.

A proof-of-concept study with a set of 22 twins showed that an epigenetic signature in buccal or cheek cells appeared only in obese twins compared to their thinner siblings. With further research, the findings could lead to a simple cheek swab test for an obesity biomarker and enable earlier prevention methods for a condition that affects 50% of US adults, the researchers said.

“Obesity appears to be more complex than normal food intake. Our work indicates that there is a susceptibility to this disease and the molecular markers for it are changing,” said Michael Skinner, a professor of biology and corresponding author of the study. Journal Epigenetics.

The study focused on twins to help disentangle the role of genetics and instead epigenetics, molecular processes that are separate from DNA but affect how genes are expressed. The finding of epigenetic signatures in cheek cells rather than fat cells also suggests that obesity signatures are likely found throughout the human system.

The systematic nature of the signature also suggests that something happened early in one twin’s life that triggered the susceptibility to obesity, Skinner added. It is also possible that it was inherited by one twin and not the other.

For the study, Skinner worked with lead author Glenn Duncan, director of the WSU-based Washington State Twin Registry, to identify 22 identical and fraternal pairs who were discordant for obesity: One sibling had a body mass index of 30 or higher, according to the Centers for Disease Control and Prevention. standard for obesity as defined by , while the other sibling was in the normal range of 25 and below.

The research team analyzed cells from cheek swabs given to the twins. In cells from twin siblings who were obese, they found similar epigenetic changes in DNA methylation regions, where molecular groups made of methane attach to DNA, controlling gene expression or turning genes on or off.

The research needs to be replicated with larger groups to develop a biomarker test for obesity, the authors said.

Duncan said the goal would be to be able to identify people earlier in life before they become obese so health care providers can help develop interventions such as lifestyle changes, medication or both.

Ultimately we want to take some form of preventative measure rather than our usual approach which is treatment. “It is a simple fact that it is better to prevent a disease, then try to treat it after it occurs.”

Glenn Duncan, director of the Washington State Twin Registry based at WSU

This research was funded by the John Templeton Foundation and the National Institutes of Health.


Journal Reference:

Duncan, G.E., etc. (2023). Epigenome-wide association study of systemic effects of susceptibility to obesity in human twins. Epigenetics.

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