Newswise — LOS ANGELES, CA: For the first time, researchers have identified two genetic variants that interact to alter the brain responses to high-calorie foods, a tie that could aid in the development of targeted treatments for obesity and overweight. Researchers at Imperial College London led by Tony Goldstone, MD, PhD, of Consultant Endocrinologist, found that two gene variants - FTO and DRD2 - influenced activity in the brain reward system when looking at pictures of high-calorie foods. The findings will be presented during an oral presentation on Thursday, Nov. 5, at The Obesity Society Annual Meeting at ObesityWeekSM 2015 in Los Angeles, CA.

What does this mean for people with obesity?

“It means they may experience more cravings than the average person when presented with high-calorie foods - that is those high in fat and/or sugar - leading them to eat more of these foods,” said Dr. Goldstone.

To conduct their study, researchers evaluated how two genetic variants near genes called FTO and DRD2 alter brain response in participants who were asked to look at pictures of either high-calorie or low-calorie foods and rate how appealing they found the pictures. This was done using a brain scanning technique called functional magnetic resonance imaging (fMRI). All cohort participants who had an fMRI scan and DNA taken were included in the study. Those participants with a variant near the FTO gene, which predisposes a person to obesity, had greater activation when looking at high-calorie foods in a part of the brain called the orbitofrontal cortex. They also found these foods more appealing, which was not seen for low-calorie foods.

“Interestingly, for the first time we also found that the activation in a part of the brain called the striatum was increased when those with the variant in FTO looked at high-calorie foods, but this depended on which variant of the other gene DRD2 they possessed. The DRD2 variant alters how the dopamine system works in the brain,” continued Dr. Goldstone.

These results suggest that part of the reason people with the FTO variant are more likely to have obesity may be because dopamine signals in their brain cause them to feel more reward and craving when presented with high-calorie foods.

“It is possible that people with these particular genetic variants may respond differently to certain treatments for obesity,” said Dr. Goldstone.

Possible treatments could include those that change how the brain processes high-calorie foods and how much people like high-calorie foods, and especially those that affect dopamine systems in the brain. This might include hormones from the gut that can act on dopamine brain cells, drugs that alter the way in which dopamine works in the brain, and even specific types of gut surgery for obesity.

“These findings help us better understand the biological basis of behaviors that may predispose some people to overeating high-calorie foods, and hence obesity,” said TOS Fellow Leah Whigham, PhD, FTOS, Executive Director of Paso Del Norte Institute for Healthy Living. “It could help us better target treatments for obesity so particular people get the most effective treatment, as individualized approaches to obesity are necessary.”

AuthorAnthony Goldstone, MD, Imperial College of London

AbstractEnergy density influences interaction between FTO and DRD2 gene variants in brain reward system responses to food evaluation

BackgroundGenetic variants near the Fat mass and obesity-associated (FTO) gene are associated with obesity and consumption of energy-dense foods. We investigated the hypothesis that FTO genotype influences dopaminergic reward systems. We examined the interaction of an FTO obesity-associated single nucleotide polymorphism (SNP) and dopamine receptor D2 (DRD2) SNP, associated with altered dopaminergic signalling, on anticipatory food reward.

Methods45 European Caucasian adults (age 19-55 years, BMI 19.1-53.1 kg/m2) had functional magnetic resonance imaging (fMRI) during evaluation of food pictures after an overnight fast, to measure food appeal and BOLD signal in brain regions involved in reward processing: nucleus accumbens, caudate, anterior insula, amygdala, orbitofrontal cortex (OFC). DNA genotyping assessed carrier status of FTO rs9939609 A and dopamine receptor D2 (DRD2) TaqA1 alleles.

>ResultsFTO A carriers had greater BOLD signal to high-energy foods in OFC in whole brain analysis, and greater high-energy food appeal rating and external eating behaviour (independent of age, gender and percentage body fat). DRD2 A1 carriers had greater reward system responses to low-energy foods, particularly in caudate and nucleus accumbens. In gene-gene-food interaction analysis, FTO A carrier status increased reward system responses to high-energy, but not low-energy foods, but only in DRD2 A1 non-carriers. Similarly DRD2 A1 carriers had greater reward system responses only to high-energy foods and only in FTO A non-carriers. Similar interactions were seen in an expanded mixed ethnicity cohort of 75 adults.ConclusionThese results support a role for the FTO gene in regulation of body weight by altering human food reward processing through influences on dopaminergic neuronal function.CitationGoldstone A. Imperial College of London. Oral abstract presentation at: The Obesity Society Annual Meeting at ObesityWeekSM 2015; November 2-6, 2015; Los Angeles, CA.

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