Researchers at Charité – Universitätsmedizin Berlin have linked a shift in the activity of a single gene during embryo development to a higher risk of overweight in women. The findings appear in Science Translational Medicine.
Obesity arises from a mix of lifestyle, socioeconomic factors, and various genetic changes. The new study adds another factor: DNA can be chemically altered to silence a gene, even without changing the underlying DNA sequence.
The team focused on the POMC gene in more than 1,100 participants. Among women with a body mass index surpassing 35, signaling obesity, the researchers observed a greater number of methyl groups attached to this gene than in women who weighed less. Methyl groups act as tiny chemical tags that regulate how genes are read, enabling the activation or suppression of genes without altering the DNA code itself.
When there was a particularly high level of methylation on the POMC gene, the odds of obesity in women rose by roughly 44 percent. Prior work has shown that the POMC gene plays a crucial role in signaling fullness.
In some instances, a disruption of the POMC gene does not reflect a change in its activity but rather a mutation that affects its function. For individuals carrying this mutation, a drug has already been approved to aid weight loss. Scientists demonstrated that this medication, which dampens appetite, also produces weight loss benefits for women with high methylation of the POMC gene.
Within about three months of starting treatment, all five participants who received the drug reported reduced hunger. They averaged a loss of seven kilograms, about 5 percent of their initial weight. Some continued treatment and kept losing weight over time.
Researchers cautioned that larger, controlled trials are needed to determine whether this therapy remains effective over longer periods and to assess its safety profile for extended use.
Other experiments indicate that certain nutrients, including betaine, methionine, and folic acid, can influence DNA methylation patterns. Yet no proven method exists to deliberately alter methylation in a controlled way at this time.
These results add to a growing area of study that links gene regulation by epigenetic marks to weight regulation, highlighting potential new approaches for addressing obesity in women who show specific methylation patterns in the POMC gene.