Researchers Use CRISPR Technology to Identify Altered Genes Causing Obesity

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Campers hold up peeled oranges in the air during a nutrition education mindful eating class at American Diabetes Association camp.

Bonnie Arbittier / Rivard Report

Campers hold up peeled oranges in the air during a nutrition education mindful eating class at American Diabetes Association camp in June 2017.

It likely comes as no surprise that a person’s genetics, diet, and built environment can contribute to their chances of becoming overweight or obese in their lifetime.

The Centers for Disease Control and Prevention has recognized the influence of genes on obesity since 2006, when studies found more than 50 genes associated with obesity, most with very small effects. In most people, no single genetic cause has been identified.

Research being conducted at the Texas Biomedical Research Institute is hoping to gain a deeper understanding of what specific genes have been altered by a person’s diet and environment, and whether those genes can be returned to a more normal functioning state through an area of research called epigenetics, the study of biological mechanisms that switch genes on and off.

“We are trying to understand whether altering the genes will cause changes at the cellular level, and if it can, can we use that information to treat the disease,” said Melanie Carless, associate scientist at Texas Biomed and principal investigator.

Texas Biomed's four-year study includes researchers from UT Health San Antonio and the University of Texas Rio Grande Valley, and is funded by a $3 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases to look into whether there are specific gene changes that fuel a person’s potential to develop obesity.

Using blood samples collected from a group of 900 Hispanic children in Texas who have a high propensity for obesity, researchers will extract DNA in order to study changes in how the body expends energy at the cellular level, and how it influences weight gain. Many of the children whose blood samples were collected are related to one another and share a similar diet and lifestyle.

"When you control for the [sample] in that way, the effect on the genes becomes more apparent," Carless said.

The CDC calls obesity an epidemic in the United States, with 40 percent of adults and 19 percent of children considered obese. Among children, however, there are disparities along ethnic groups. Hispanic children have the highest rate of obesity at 26 percent, followed by black children at 22 percent, and Caucasian children at 14 percent.

“We need to understand how obesity develops at a young age and the impact this might have on health later in life,” Carless said.

Combining physical data such as caloric intake, energy expenditure, and glucose levels with another factor called DNA methylation, a biochemical process in which methyl groups are added to DNA in a way that changes a gene's expression, will help researchers identify specific pathways that are involved in the development of obesity.

After identifying cellular-level changes, the researchers will utilize CRISPR technology, a genome editing system that targets specific stretches of genetic code to edit DNA at precise locations. This will show whether the methylation of specific genes is related to increase risk for obesity, and whether modifying them will help the cells return to a more normal state of functioning, Carless said.

“Most people are very aware of the fact that your lifestyle does impact your risk for obesity. This [study] is the first step in understanding the biology that actually leads to obesity in order to solve it by helping researchers understand what to treat based on the obstructed pathways that affect an individual, their propensity toward obesity, and help to develop more individualized treatment,” Carless said.

The outcome of the research could lead to more targeted treatments to aid weight loss and to help maintain a health weight, she said.

“It’s difficult to tell everyone to go on a diet, but if you can tell one person to stop eating a certain type of food and that will help, those sorts of things might be more easily manageable,” Carless said.

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