Epigenetic Changes Help Explain Link Between Genetics and Obesity, Study Observes

Epigenetic Changes Help Explain Link Between Genetics and Obesity, Study Observes

Although obesity is mostly related to unhealthy habits, new research in adolescents suggests that epigenetic changes — those that affect gene expression without altering the DNA sequence — in obesity-related genes also may contribute to the disease.

The study with that finding, “Association between DNA methylation in obesity-related genes and body mass index percentile in adolescents,” was published in the journal Scientific Reports.

According to the Centers for Disease Control and Prevention’s National Center for Health Statistics, 17% of children living in the U.S. in 2014 were obese, representing about 12.7 million children and adolescents.

Scientists believe that 40% to 70% of the variation in obesity cases is actually heritable, meaning that genetics could be contributing to obesity. But while previous genome-wide association studies identified a large number of obesity-related genes, these can explain only a limited proportion of the variances in obesity.

Researchers from Pennsylvania State University hypothesized that another type of genetic mechanism — called epigenetics — could help explain the link between genetics and obesity.

Epigenetic changes are modifications that affect how genes are produced — sometimes having major effects on physical traits — without actually changing their DNA sequence.

DNA methylation is one of the most common epigenetic mechanisms, in which methyl groups are added to DNA to prevent other proteins from getting near the gene. Consequently, the machinery needed for producing a protein from that gene cannot do its job properly, and levels of the protein drop considerably.

While this is a natural process that occurs during development and cellular differentiation, DNA methylation also has been associated with diseases such as chronic diseases and cancer.

To determine if DNA methylation in obesity-related genes could help explain the relationship between obesity and genetics, the team examined these epigenetic alterations in 263 children and adolescents included in the Penn State Child Cohort follow-up exam.

Participants had a mean age of 16.7 years and were mostly non-Hispanic white (79%) and male (55.95%). According to their body mass index (BMI) — a calculated measure of body fat — they were divided into underweight underweight (1.9%), normal weight (61.6%), overweight (20.5%) and obese (16%).

The team looked at specific locations within the genes called cytosine-phosphate-guanine sites, where methylation patterns normally are found. Among the 103,466 sites examined, 5,669 were associated with BMI, and 28 were within 11 obesity-related genes.

Interestingly, the team found a novel site in the SIM1 gene that had one of the strongest associations with obesity. For each 10% increase in methylation in this site, an increase of 7.2 points in BMI was observed.

The SIM1 gene is responsible for neuronal differentiation in a specific area of the brain that is critical for food intake regulation, and has been implicated in obesity in children.

Overall, “this evidence suggests that DNA methylation change is related to obesity, even in healthy adolescents. Such an early life change may be associated with elevated cardiometabolic risk in adulthood,”  investigators concluded.

However, they pointed out that “it is also biologically plausible that alternation in DNA methylation was driven by presence of obesity,” and that additional studies are needed to “provide deeper insight into the causal direction of the association, as well as possible origins of the variation in DNA methylation levels.”

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.

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