A variety of factors can affect a person's weight, including personal habits like what they eat and how much activity they get, and biological traits like genetics. Scientists have now found that epigenetic characteristics, or modifications to the genome that alter how genes are expressed but do not change the genetic sequence, can also have a significant impact on an individual's likelihood of becoming overweight. This research, which was reported in Science Translational Medicine, highlighted the importance of epigenetic tags on a gene called POMC, which are established during development.
Although there is disagreement over how excess body weight should be defined in people, and whether obesity directly increases the risk of death, there is evidence that people who are overweight, and particularly those who are severely overweight, are at greater risk for health disorders including cancer, diabetes, and cardiovascular disease. Rates of obesity are also increasing around the world, according to the World Health Organization.
Previous work has shown that some small variations in genes can influence a person's body weight and obesity risk. In twin studies, anywhere from 40 to 70 percent of study subjects have similar body mass indexes, and those genetic variations do not fully account for the heritability seen in body weight.
Now, an epigenetic factor has been revealed, which can help explain the heritability factor. This study showed that in women, the risk of being overweight is increased by around 44 percent if there is an abnormally high level of methyl groups attached to the POMC gene. This gene is expressed in hypothalamic neurons, which are crucial to the feeling of being full after eating, or satiety. Methyl groups are a very common epigenetic tag that can alter gene expression. Identical twins tended to carry the same POMC methylation patterns compared to fraternal twins, suggesting that the POMC gene is methylated in this way very early on during development.
The scientists determined that when women had a BMI over 35, in the severely obese category, they had more methyl groups on their POMC gene compared to women with BMIs in the normal range. The researchers were interested in how these methylation patterns are established. They suggested that the system for methylating DNA is quite stable, and that variability appears to arise at random. We also don't yet know what influences the degree of methylation of the POMC gene.
The investigators did recruit four women and one man who were severely obese, and treated them with a drug that has been used for people who carry a mutation in POMC. All five individuals were experiencing less hunger within three months of starting the treatment, and had lost about five percent of their body weight.
"These findings show, for a start, that a POMC gene that has undergone epigenetic changes can in fact potentially be addressed through medication," said study leader Professor Peter Kühnen, Director of the Department of Pediatric Endocrinology at Charité,
"Further large controlled studies will be needed to show whether treatment with this drug would also be effective over a longer period, and if so, how effective and how safe this type of treatment is. Overall, though, a medication like this would still need to be just one piece of a holistic treatment strategy."
The researchers also don't yet know why this methylation pattern is only observed in women.
Sources: Charité – Universitätsmedizin Berlin, Science Translational Medicine
