Jan Bressler, Ph.D.

assistant professor of epidemiology, Human Genetics Center, School of Public Health (SPH)

Research Work: DNA Methylation Profiles in a Polygenic Mouse Model of Diet-Induced Obesity

Jan Bressler, Ph.D.

Obesity among children and adults represents a growing epidemic and a serious public health problem in America. In fact, the latest figures from the National Center for Health Statistics report that more than 12 and a half million children and adolescents ages 2-19 years are overweight, and more than 66 million adults are obese.

Although likely caused by overeating and physical inactivity, obesity is a complex issue related to lifestyle, environment and genes.

Research by Jan Bressler, Ph.D., delves into how genetics plays a role in obesity. Specifically, she is interested in DNA methylation profiling patterns.

“Although the results of twin and adoption studies provide strong support for a genetic influence on body weight, major genes contributing to common obesity have not yet been identified,” said Bressler.

However, one type of obesity syndrome that has been linked to genetics is Prader-Willi syndrome – a complex disorder caused by a missing gene or genes on chromosome 15 inherited from the father. The syndrome causes poor muscle tone, short stature, incomplete sexual development, learning disabilities, behavioral problems and a constant feeling of hunger that can lead to overeating and ultimately obesity.

Bressler said Prader-Willi syndrome is an example of a disease that involves genomic imprinting where the genetic abnormality comes from one parent, “while the copy inherited from the other parent is silenced,” she explained. “An important feature of imprinted genes is that the identity of the two parental chromosomes must be distinguished throughout development, and this is currently believed to involve epigenetics, often defined as heritable changes in gene expression that are not encoded in the DNA sequence itself.” DNA methylation – where a methyl group is added to DNA – is a form of epigenetics.

“DNA methylation usually leads to gene silencing and has been associated with the inactive copy of most imprinted genes,” Bressler said. Bressler’s research into Prader-Willi syndrome led to her further study of the impact of DNA methylation profiling.

“Most of the difference in adiposity, or the amount of body fat, between individuals is determined by multiple genes with variation in any single gene producing only a moderate effect,” Bressler said. “The modulation of gene expression in obese individuals is probably due to changes in gene regulation when compared to those whose weight is in the normal range. My long-term goal is to evaluate whether any of these changes can be detected as modifications in DNA methylation patterns over time.”

As a step toward approaching her goal, Bressler currently is studying the effects of a high-fat diet versus a normal-fat diet fed to two groups of wild-type mice.

“DNA from various target organs was prepared at several time points during the progression of diet-induced obesity, and experiments in which the methylation status of thousands of genes is assessed at the same time using microarray technology are currently underway,” Bressler said, adding that she hopes this mouse model will increase her understanding of the methylation patterns of diet-induced obesity.