Two Genes May Alter Brain Responses to High-Calorie Foods

Researchers have identified 2 genetic variants that interact and alter the brain’s responses to high-calorie foods, new data suggest.

Some people may be more prone to obesity because dopamine signals in their brains trigger more feelings of reward and craving than in other people when presented with high-calorie foods, researchers reported at ObesityWeek 2015. The discovery of these genetic variants that affect these brain responses, however, may aid in the development of targeted treatments for obese and overweight individuals.

“Future therapies could be more targeted to an individual’s predisposing factors, including genetics,” said study investigator Tony Goldstone, MD, PhD, who is a consultant endocrinologist at Imperial College London in the United Kingdom.

Dr Goldstone and colleagues have found that 2 gene variants — FTO and DRD2 — influence activity in the brain reward system when looking at pictures of high-calorie foods. Subsequently, some people may experience more cravings than the average person when presented with high-calorie foods, such as those high in fat and sugar. 

The study included 45 European Caucasian adults aged 19 and 55 years with BMIs ranging from 19.1 to 53.1.

“Genetic variants near the FTO gene have the strongest link to obesity in the general population. Our study reveals that such a variant may in part contribute to overconsumption of energy-dense foods by altering how the brain responds to food cues in the environment through modification of brain dopaminergic systems,” Dr Goldstone told Endocrinology Advisor.

“It is possible that people with these particular genetic variants may thus respond differently to certain treatments for obesity that modify such systems, including appetitive hormones from the gut such as ghrelin and GLP-1, drugs acting on dopamine receptors or reuptake in the brain, and even particular sorts of bariatric surgery for obesity.”

As part of their investigation, the researchers used functional magnetic resonance imaging (fMRI) to see how FTO and DRD2 alter brain response in individuals who were asked to look at pictures of either high-calorie or low-calorie foods and rate how appealing they found the pictures.

The investigators analyzed the DNA of each participant and found that those participants with a variant near the FTO gene had greater activation when looking at high-calorie foods in the orbitofrontal cortex. They also found these foods more appealing, which was not seen for low-calorie foods.  

Dr Goldstone said these findings are notable because it is the first time a study has demonstrated activation is increased in the striatum when those with the variant in FTO look at high-calorie foods. 

However, this depended on which variant of the other gene, DRD2, they possessed. The DRD2 variant altered how the dopamine system worked, Dr Goldstone noted, and the researchers found that these results were similar in an expanded mixed ethnicity cohort of 75 adults. 

“Genetic variants that predispose to obesity may do so through altering how the brain responds to food in the environment. Patients who are obese need others to be understanding of such findings to aid de-stigmatization and appreciation of why interventions whether pharmaceutical or surgical are needed,” said Dr. Goldstone.

Leah Whigham, PhD, who is the executive director of Paso Del Norte Institute for Healthy Living in El Paso, Texas, as well as a member of The Obesity Society (TOS), said these findings will help clinicians better understand the biological basis of behaviors that may predispose some individuals to overeating high-calorie foods. 

In addition, these findings are an important step toward the development of more targeted treatments for obesity, she noted. 

“This study is another important part of the picture with regards to causes and potential treatments for obesity. We need a better understanding of how genetics and our environment can interact to influence the brain’s responses to food and drivers of food intake. This study provides another important piece to that puzzle,” Dr Whigham told Endocrinology Advisor. 

“This research illustrates that there are important internal controls at play when it comes to regulation of food intake and body weight, and can help lay the foundation for future treatments. Obesity is a complex disease and we need to address those complexities when identifying ways to help people who struggle with obesity.”

Reference

1. Yiorkas A, Prechtl C, Sleeth M, et al. Abstract T-OR-2065. Energy density influences interaction between FTO and DRD2 gene variants in brain reward system responses to food evaluation. Presented at ObesityWeek; November 2-6, 2015; Los Angeles, CA.