Becky McCall

September 24, 2015

In pairs of identical twins, where one is lean and the other heavy, the lean twin better inhibits her impulses when shown pictures of high-calorie food compared with her heavier counterpart, according to a new brain-imaging study of identical but body mass index (BMI)–discordant twins.

Findings of the study, discussed at the European Association for the Study of Diabetes (EASD) 2015 Meeting last week, also suggest that previously observed altered brain responses to food cues in general obesity are likely influenced by genetic rather than environmental factors.

This stems from the observation that the identical twin pairs showed similar responses in the brain's reward center to pictures of food generally.

But the leaner twin showed greater inhibitory control mediated by the orbitofrontal cortex in response to high-calorie food cues, and the latter is therefore likely "a result of environmental influence," pointed out the presenter of the research, Stieneke Doornweerd, a PhD student from VU University Medical Center, Amsterdam, the Netherlands.

Commenting on the work, session moderator Dr Martin Heni, MD, from University Hospital Tuebingen, Germany said: "This was a really interesting study that shows genetics are important to determine response to food in general, but environmental factors seem to determine responses to high-calorie food, which causes weight gain.

"Indeed, environmental factors are responsible for the obesity pandemic we see now," he added.

Reward and Impulse Controls in Lean and Obese Co-twins

Ms Doornweerd said that their study aimed to disentangle some of the genetic and environmental factors that affect brain responses to food, given the rapid surge in obesity, which indicates that the environment is having a powerful influence.

"We know the causes are multifactorial and complex and that genetic factors, which account for 40% to 70% of differences in BMI, and environmental factors are involved."

Excessive eating in obese people is considered to be due to a response to food cues in the reward center of the brain, but altered responses in the area involved in inhibition of impulse — the orbitofrontal cortex — are also thought to be involved.

Previous functional MRI studies have shown increased responses to visual food pictures in the reward center of the brain in obese compared with lean people.

"But there is also a decreased response to food images in the orbitofrontal cortex in obese vs lean subjects, and this relates to impulse control, suggesting that obese people have high craving for food but also that they have a low ability to inhibit their eating," explained Ms Doornweerd.

Monozygotic but Discordant Twin fMRI Study

Ms Doornweerd said her study is the first to look at the impact of environmental factors, independent of genetic factors, on altered brain responses to food cues in discordant monozygotic twins.

A total of 16 female, monozygotic twin pairs were recruited from the Netherlands Twin Registry. They had a BMI discordance of at least 3 kg/m2. "This is very rare," she pointed out.

Patients were categorized as leaner (mean weight 68.9 kg) and heavier (80.5 kg). BMI was 24.4 kg/m2 and 28.4 kg/m2 for leaner and heavier co-twins, respectively. Basal metabolic rates were similar.

After functional MRI, indirect calorimetry was used to measure basal metabolic rate during a 4-hour visit conducted after an overnight fast. Subjective ratings of appetite and hunger were recorded, and follow-up phone calls assessed 24-hour recall of food intake over the following 2 weeks.

The imaging assessed brain responses to food cues comprising "all food" (low- and high-calorie combined), high-calorie food (cake, hamburgers), low-calorie food (fruit), and nonfood images (trees, bricks). The assessment focused on areas of the brain involved in eating.

Leaner Twin: Better Response in Inhibitory Orbitofrontal Cortex

Lean and heavy co-twins showed no differences in brain responses in the reward center to pictures of "all foods" combined in MRI.

"This surprised us," Ms Doornweerd pointed out, as this differs from what has been seen in prior studies in singleton lean vs obese individuals.

And also contrary to expectation, when high-calorie pictures were shown, relative to the leaner co-twin, the heavier one did not show a greater brain response.

"However, when the leaner co-twin was assessed relative to the heavier one, we found a higher brain response in the orbitofrontal cortex — a region involved in inhibitory control of impulses," she explained.

Food recall showed that heavier co-twins did not have an increased energy intake, but they did have an increased fat intake.

The fact that these findings were seen in monozygotic twins implies that they are independent of genetic effects and must be due to other factors, the researcher reinforced.

"The results suggest that previously observed altered brain responses to food cues in obesity are likely influenced by genetic factors," noted Ms Doornweerd. "But the higher inhibitory control mediated by the orbitofrontal cortex in lean subjects is a result of environmental influence."

She added that further studies are needed to elucidate which particular environmental factors are responsible.

Is This an Effect of the Obesity?

Commenting on the study, Stephanie Amiel, MD, RD, Lawrence Professor of Diabetic Medicine, King's College London, United Kingdom,  said: "This is a beautiful study. You've looked at the fasting state, so I hope you will go on to look at the fed state, too. Although this might be a cause of obesity through influencing interest in food, there's also a possibility that this is an effect of the obesity."

Dr Heni added that the frontal area of the brain was important for inhibitory control. "We believe that altered activity here prevents inhibition of food intake. In this study, in fasting conditions, you could speculate that these [obese] subjects tend to eat more."

"The frontal areas of the brain are sensitive to metabolic disturbances in the body including insulin and [glucagonlike receptor 1] GLP-1. Maybe this change is secondary to a metabolic alteration?" he concluded.

The study was supported by Netherlands Organization for Scientific Research. Ms Doornweerd, Dr Amiel, and Dr Heni have declared no relevant financial relationships.

European Association for the Study of Diabetes (EASD) 2015 Meeting. Abstract 141, presented September 16, 2015.


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