Is obesity all in the brain?

Thursday, September 06, 2018. Author Dr. Haran Sivapalan

Is obesity all in the brain?

"What causes obesity?"

Pose this question to the average person on the street, and they may reply, "Poor diet and a lack of physical exercise".

While this is undoubtedly true, lots of research is also starting to implicate behavioral, psychological, and personality factors in the development of obesity. For example, it's well established that obesity is associated with neuroticism, a personality trait that describes a person's tendency to experience negative emotions. Other studies link obesity to poorer executive function – a measure of someone's ability to plan, pay attention and inhibit impulsive behaviors when completing a cognitive task.

Genes, brains, and body weight

Of course, our behaviors, thoughts, and personalities all originate from the most complex organ in the body – the brain. The difference between an overweight and a healthy weight person, may not solely result from their contrasting dietary and exercise habits, but also from differences in the structure and activity of their brains. 
Furthermore, some of these brain differences are heritable: that is, they pass on from generation to generation and are underpinned by variation in our genes. Looking at the bigger picture, it may partly be the case that genes cause changes in the brain, which, in turn, alter our behaviors, ultimately leading to poorer dietary and exercise habits and the development of obesity.

A prime example of this is with the FTO ‘obesity gene' – one of the gene variants we test and research at FitnessGenes. The ‘A' allele of this gene confers an increased risk of obesity, with people carrying two copies (i.e., the AA genotype) being 70% more likely to be obese. It's thought that the FTO gene alters the brain's reward circuity: the brain's network that lights up in response to food, sex, drugs, and even Facebook likes.

Studies suggest that, in ‘A' allele carriers, these areas of the brain respond differently to the sight of high-calorie foods. The reward circuits are also more reactive to ghrelin, a hormone that signals hunger. Taken together, such brain changes increase the likelihood of someone feeling hungry, feasting on junk food and subsequently gaining weight. Clearly, in this scenario, the FTO gene exerts its influence on bodyweight via changes in the brain and behavior.

But just how much of our wider genetic vulnerability to obesity is also manifested in the brain? According to a new study, published in the journal Proceedings of the National Academy of Sciences (PNAS), the answer is: quite a lot.

What did the study investigate?

Researchers analyzed the data from people enrolled in the Human Connectome Project, a large, ambitious study that aims to accurately map the networks of neurons in the human brain.  

In particular, the team looked at subjects' BMI (Body Mass Index), cognitive and personality test results, and brain imaging data, including the size of various areas of the brain. This allowed them to investigate any link between body weight and changes in brain structure and function.

But how do genes fit in here? 

Of the 895 subjects examined, there were 111 pairs of identical twins and 188 pairs of non-identical twins and siblings. Identical twins are always of interest to scientists because they essentially share 100% of their DNA.

By contrast, non-identical twins and siblings share, on average, about 50% of their DNA.
If identical (or monozygotic) twins show more similarity on a trait (e.g., BMI, memory score, or size of a brain structure) compared to non-identical (or ‘dizygotic') twins, then it can be inferred that genes probably have a strong influence on that trait.

By contrast, if identical and non-identical twins turn out to be equally similar on traits, despite identical twins sharing more DNA, then it's likely that environment plays a stronger role.

Twins therefore allow scientists to tease apart the relative role of genes and environmental factors; also known as nature versus nurture.

Accordingly, in this study, the team could calculate the relative contribution of genes and environment to BMI and also to cognitive test scores and brain changes.
Finally, using complex statistical methods, they could see whether there was any genetic overlap between these traits, i.e., whether it was the same genetic factors contributing to high BMI, cognitive test scores and obesity-related brain changes. 

What did the study show?

Higher BMI was linked to poorer spatial reasoning, verbal memory and greater impulsivity on cognitive tests. When it came to brain changes, obesity was associated with reduced thickness of a part of the brain called the right prefrontal cortex (rPFC). The rPFC has long been implicated in the control of food intake. Intriguingly, people with damage to this brain area can even go on to develop the so-called ‘Gourmand syndrome' characterized by a passion for eating fine foods!

Such brain changes are consonant with a model of obesity termed ‘the right brain hypothesis' – a theory which holds that reduced function in the right frontal lobe may cause a loss of control of food intake, overeating and lack of physical activity.

Another brain area linked to obesity is the amygdala – an almond-shaped structure located deep in the brain which is responsive to food-related cues: the sights, smells and sounds of foods. Higher BMI was associated with a larger left amygdala, supporting the notion that the brain is more responsive to food cues in obesity.
Interestingly, there was significant genetic overlap between these brain changes, cognitive test scores, and high BMI – the same genetic factors contributed to all three measures.

There are two ways to interpret this finding. If you accept the analogy, imagine a sunny day causing an increase in ice cream sales and a rise in swimming pool admissions. Here, ice cream sales are not directly related to swimming pool admissions. Instead, both are downstream effects of the sunny weather.  Similarly, it could simply be the case in this study that the same genes which confer risk to obesity also happen to cause changes in the brain and cognitive test scores.

The authors, however, favor a different interpretation. Continuing the analogy, they argue that a sunny day causes increased swimming pool admissions, which in turn leads to greater ice cream sales. In other words, they believe that genes underlie brain changes AND it is these very brain changes that cause people to overeat and become obese.

Under this view, the fact that two identical twins or two siblings are both obese is due to the fact that they have both inherited similar brain changes. 

It's a fascinating theory and one that warrants further research. This is especially true in light of the finding that 75% of obesity-related genes are chiefly expressed in the brain. Some of these genes include NMB, MC4R, FTO, all of which affect eating behavior and are analyzed here at FitnessGenes.

I hope you enjoyed this blog.  Please read my other articles and let me know if you have any questions.

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