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Double Take: How Twins Are Unlocking the Molecular Mysteries of Obesity

Washington State University researchers have found an epigenetic signature in the cheek cells of obese twins that differs from their non-obese siblings, pointing to a molecular predisposition to obesity.

Researchers have discovered molecular markers in cheek cells that could predict obesity, potentially allowing for early interventions and a shift towards preventative healthcare measures.

A susceptibility to gain weight may be written into molecular processes of human cells, according to a research study from Washington State University.

The proof-of-concept study with a set of 22 twins found an epigenetic signature in buccal or cheek cells appearing only for the twins who were obese compared to their thinner siblings. With more 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 U.S. adults, the researchers said.

“Obesity appears to be more complex than simple consumption of food. Our work indicates there’s a susceptibility for this disease and molecular markers that are changing for it,” said Michael Skinner, a WSU professor of biology and corresponding author of the study published in the journal Epigenetics.

Epigenetic Signature and Obesity

The study focused on twins to help eliminate the role of genetics and instead focus on epigenetics, molecular processes that are separate from DNADNA, or deoxyribonucleic acid, is a molecule composed of two long strands of nucleotides that coil around each other to form a double helix. It is the hereditary material in humans and almost all other organisms that carries genetic instructions for development, functioning, growth, and reproduction. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA).” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>DNA but influence how genes are expressed. The fact that the epigenetic signature was found in cheek cells rather than fat cells also suggests that the obesity signature is likely found throughout the human system.

The signature’s systemic nature also suggests that something may have occurred early in one twin’s life that triggered obesity susceptibility, Skinner added. It’s also possible that it was inherited by one twin and not the other.

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

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

Future Research and Prevention

To establish a reliable biomarker test for obesity, the study would need to be conducted on a larger scale.

The goal would be able to identify people earlier in life before they become obese so healthcare providers might help create interventions such as lifestyle changes, medication, or both, said Duncan.  

“Ultimately we would like to have some kind of preventative measure instead of our usual approach which is treatment,” he said. “It’s a simple fact that it’s better to prevent a disease than to try to treat it after you have it.”

Reference: “Epigenome-wide association study of systemic effects of obesity susceptibility in human twins” by Glen E. Duncan, Ally Avery, Millissia Ben Maamar, Eric E. Nilsson, Daniel Beck and Michael K. Skinner, 23 October 2023, Epigenetics.
DOI: 10.1080/15592294.2023.2268834

This research was funded by the John Templeton Foundation and the National Institutes of HealthThe National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>National Institutes of Health.

Source: SciTechDaily