Obesity stands as a multifaceted health concern affecting millions worldwide. While diet and lifestyle play pivotal roles, researchers are now looking much deeper to determine if susceptibility to obesity could be identified at a molecular level within human cells.
In a recent study led by distinguished biology professor Michael Skinner at Washington State University (WSU), a comprehensive twin study was undertaken to probe the epigenetic factors associated with obesity. Their findings uncovered specific DNA methylation regions (DMRs) intricately connected to metabolic and dietary influences, offering crucial insights into the complexities of obesity.
While not the only study we have featured that examined twins and their links to obesity, this investigation sought to uncover potential epigenetic connections associated with metabolic and dietary factors in relation to obesity. Published in the journal Epigenetics, the investigation included 22 sets of twins (both identical and fraternal) discordant on obesity status recruited from the community-based Washington State Twin Registry.
The scientists discovered a unique mark in cheek cells that only appeared in the twins with obesity and not in their slimmer siblings. This finding suggests the possibility of a simple cheek swab test for an obesity marker, offering a way to find and prevent this condition that affects half of adults in the United States.
According to Michael Skinner, the lead author for the study, “Obesity is more than just eating; our work shows there’s a vulnerability for this disease and changing molecular signs for it.”
The study focused on twins, in particular, to observe the impact of factors beyond genetics since twins share similar DNA. Differences observed between twins often stem from environmental influences and epigenetic changes—processes occurring outside DNA, such as DNA methylation, histone modifications, and chromatin remodeling. Unlike genetic alterations, these epigenetic shifts don’t change DNA but can affect how genes function within cells.
Here, researchers obtained DNA from participants who used buccal brushes to collect cheek cells at home. They then utilized Methylated DNA Immunoprecipitation (MeDIP) to target DNA methylation, followed by sequencing and computational analysis to pinpoint differentially methylated regions (DMRs) and associated pathways. Additionally, they employed Weighted Gene Coexpression Network Analysis (WGCNA) to confirm the gene expression patterns found across various genomic sites.
The analysis was able to identify a unique biomarker associated with obesity susceptibility. Because the mark was found in the DNA of the cheek cells rather than fat cells, this indicates its presence throughout the body. Moreover, the systemic nature of this mark suggests that something might have happened early in life that triggered obesity or that it could have been potentially inherited by one twin and not the other.
The twin sets that researchers worked with had one twin with a high body mass index (BMI) to indicate obesity and the other twin with a normal BMI. Analysis of cheek cell samples from the obese twins showed similar changes in specific regions of DNA, influencing gene activity. The scientists suggest that more research with larger groups is needed to develop a reliable test for obesity.
The ultimate aim is to identify people at risk of obesity early on so healthcare providers can help with interventions like lifestyle changes or medications before obesity becomes a problem. According to Glen Duncan, the director of the study, “It’s better to prevent a disease than to treat it after you have it.”
Source: Glen E. Duncan, et. al. Epigenome-wide association study of systemic effects of obesity susceptibility in human twins. Epigenetics. October 23, 2023.
Reference: Sara Zaske, Epigenetic signature for obesity found in study of twins. WSU Insider. November 1, 2023.
