Two gene variants influence cravings for high-calorie foods

LOS ANGELES — Two variants near the FTO and DRD2 genes are associated with the preference for high-calorie, energy-dense foods in adults, according to study findings presented at ObesityWeek.

Tony P. Goldstone, MD, PhD, a consultant endocrinologist at Imperial College London, said adults with a variant near the FTO gene experienced greater activation in the orbitofrontal cortex region of the brain, as measured by functional MRI, when looking at pictures of high-calorie foods in a study. The same adults also found those foods more appealing when compared with their reactions to nonfood pictures, he said.

Tony P. Goldstone

“We have an environment that conspires against our biology that causes us to overeat,” Goldstone said while presenting his findings. “And what we’re trying to do is look at factors that may modify eating behavior, particularly food reward and other addictive behaviors.”

Using functional MRI, Goldstone and colleagues analyzed the interaction of an FTO-associated single nucleotide polymorphism (SNP) and dopamine receptor D2 (DRD2) SNP on the anticipation of food reward in 45 healthy white adults aged 19 to 55 years (mean age, 31.8 years; 55.6% women; 44.4% lean; 31.1% with overweight; 24.4% with obesity). Within the cohort, 39% were positive for the FTO gene variant; 30% were positive for the DRD2 variant; carrier status of the two gene variants was established through DNA genotyping. After an overnight fast, participants underwent functional MRI while evaluating various food and nonfood pictures. Researchers measured blood oxygen level dependent (BOLD) signaling in the nucleus accumbens, caudate, anterior insula, amygdala and orbitofrontal cortex.

In whole-brain imaging, researchers found that carriers of the FTO variant had a greater BOLD signal in response to high-energy foods in the orbitofrontal cortex, as well as a greater high-energy food appeal rating. Results persisted after adjustment for age, sex and body fat percentage.

Carriers of the DRD2 variant had greater reward system responses to low-energy foods, Goldstone said, that were seen primarily in the caudate and nucleus accumbens regions of the brain.

In a gene-gene-food interaction analysis, Goldstone said only adults who were positive for the FTO variant, but also negative for the DRD2 variant, expressed increased reward responses to the high-calorie food pictures. Adults who were positive for the DRD2 variant had greater responses to high-energy foods, but only when they were also negative for the FTO variant, he said.

Goldstone said similar results were seen in an expanded, multiethnic cohort that included 75 adults (mean age, 32.9 years; 61.3% women; 60% white; 37.3% lean; 34.7% with overweight; 28% with obesity).

In a statement regarding the study findings, Leah Whigham, PhD, FTOS, executive director of the Paso Del Norte Institute for Healthy Living in El Paso, Texas, said the results help researchers better understand the biological basis of behaviors that may predispose some people to overeating high-calorie foods.

“[The results] could help us better target treatments for obesity so particular people get the most effective treatment, as individualized approaches to obesity are necessary,” Whigham said in a press release. – by Regina Schaffer

Reference:

Goldstone AP, et al. OR #2065. Presented at: ObesityWeek; Nov. 2-6, 2015; Los Angeles.

Disclosure: Goldstone reports no relevant financial disclosures.