Newswise — Apart from lifestyle factors, genetics also plays a part in determining whether individuals become overweight. However, genes alone cannot entirely account for the inherited inclination to accumulate excess weight. A recent study conducted by Charité – Universitätsmedizin Berlin and published in Science Translational Medicine* sheds light on a specific gene linked to satiety, where the formatting of the DNA code is implicated in a slightly higher risk of excess body weight, particularly in women. This "epigenetic marking" is established during the embryonic stage, indicating its early influence on weight regulation.
Overweight individuals, especially those with severe obesity, face an elevated risk of numerous serious diseases, including cardiovascular disease, diabetes, and cancer. This escalating health concern is becoming more prevalent worldwide. The number of overweight individuals is on the rise globally. In the European Region, data from the World Health Organization indicates that nearly two out of three adults (59 percent) are either overweight or obese, underscoring the urgency for effective measures to address this growing public health issue.
The likelihood of individuals becoming overweight is determined by a combination of genetic predisposition and lifestyle factors. Genetic influence plays a significant role, as evidenced by the body mass index (BMI) similarity in identical twins, which ranges from 40 to 70 percent. Surprisingly, even when identical twins are raised in different families, their BMI still exhibits notable similarities. Scientists have identified various genetic variants that impact body weight and the risk of developing obesity. However, despite considering all these factors collectively, they are unable to fully account for the observed heritability. Consequently, researchers have started to explore the presence of additional non-genetic factors that contribute to a person's inclination to gain excess weight. These investigations aim to provide a more comprehensive understanding of the complex interplay between genetics and other factors in the development of obesity.
Satiety gene is not altered, but formatted
In their recent study, researchers, led by Prof. Peter Kühnen, Director of the Department of Pediatric Endocrinology at Charité, have uncovered a significant factor. They have identified a link between the number of methyl groups attached to the POMC (pro-opiomelanocortin) gene, responsible for regulating satiety, and women's risk of becoming overweight. The study reveals that women with an abundance of methyl groups experience a 44 percent increase in the likelihood of being overweight. Methyl groups are minuscule chemical units that the body utilizes to tag the letters in the DNA code, either activating or deactivating genes without altering the underlying DNA sequence. In simpler terms, it's like highlighting a specific section of text without rewriting the entire content. This phenomenon, known as epigenetic marking, represents a form of "DNA formatting" with potentially significant implications for weight management and health.
In their study, the research team meticulously analyzed the epigenetic "formatting" of the POMC gene in a substantial cohort of over 1,100 individuals. Notably, they observed a higher presence of methyl groups attached to the satiety gene in obese women with a BMI exceeding 35, compared to women with normal body weight. Prof. Peter Kühnen highlights that this increase in the risk of obesity, approximately 44 percent, is comparable to the effects seen with individual gene variants. However, he emphasizes that socioeconomic factors wield a much more substantial influence, as they can amplify the risk of obesity by two to three times.
Interestingly, the researchers have not yet determined the reason why the methylation effect only manifests in women and not in men. Further investigations and studies are required to uncover the underlying mechanisms driving this gender-specific difference in epigenetic regulation of the POMC gene. Nevertheless, these findings provide valuable insights into the complex interplay of genetic and epigenetic factors contributing to weight-related conditions in women.
By conducting a thorough investigation, encompassing over 15 sets of identical and fraternal twins, the researchers have illuminated the crucial timing of the "formatting" process for the POMC gene. By comparing the methylation patterns of these twin pairs, the team made a fascinating revelation. In the majority of identical twins, the "formatting" of the satiety gene exhibited striking similarity, suggesting a robust correlation in their epigenetic marking. However, in fraternal twins, this correlation proved to be considerably weaker.
What influences formatting?
The level of methylation that the satiety gene undergoes, and consequently the risk of a person becoming overweight, can be influenced by various factors. Previous studies have suggested that the availability of specific nutrients providing methyl groups may have an impact on epigenetic processes. Among these nutrients are betaine, methionine, and folic acid, which are commonly obtained through dietary intake. Recently, Charité researchers developed a novel technique using individual human stem cells to replicate and study the methylation pattern's determination during embryonic development and how it is influenced by nutrients in a laboratory setting. This method offers valuable insights into the role of nutrition in epigenetic regulation.
"In our studies, along with other research, we have found that nutrients like folic acid and betaine have only a limited impact on the extent of methylation," states Kühnen. "The 'DNA formatting system' appears to be highly stable overall, with cells compensating for minor changes in nutrient availability. However, there are indications that the variability in this 'formatting' occurs randomly. Consequently, as of now, it is not feasible to externally control or influence whether an individual will have more or less methylation in the POMC region."
Medications may help
In theory, women who face an increased risk of obesity due to methylation of the POMC gene could potentially benefit from medications aimed at aiding weight loss, as indicated by initial studies involving four severely obese women and one man with the same "formatting" of the satiety gene. These subjects were administered a specific drug designed to reduce hunger, which has already received approval for treating obese patients with a POMC gene mutation. Remarkably, within three months of commencing the treatment, all five patients experienced a decrease in hunger and shed an average of seven kilograms, approximately five percent of their body weight. Some participants continued the treatment and continued to lose weight even further. These findings suggest the promising potential of such medications in addressing obesity risks associated with the methylation of the POMC gene. However, further research and clinical trials are necessary to confirm the safety and efficacy of this approach on a larger scale before broader recommendations can be made.
According to Kühnen, these findings provide initial evidence that medication can potentially address a POMC gene affected by epigenetic changes. However, to draw more definitive conclusions, further extensive and controlled studies will be necessary to determine the drug's effectiveness over an extended period and to evaluate its safety. It is crucial to understand how well this treatment works and whether it can be safely employed. It's important to note that while such medication shows promise, it would likely be just one component of a comprehensive treatment strategy for addressing obesity. A holistic approach would involve considering multiple factors, including lifestyle modifications, dietary changes, and possibly other therapeutic interventions in conjunction with the medication to achieve the best outcomes for individuals at risk of obesity due to POMC gene methylation.
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