A load on the mind

(Published in Medical Imaging Technology magazine, issue 15)

GFPneuron

Human neuroimaging and animal studies are beginning to build evidence that serotonin and dopamine- mediated mechanisms have an effect on food intake and play an important role in the pathophysiology of obesity – possibly suggesting that the condition could be caused by a physiological addiction to fatty food. Leipzig University’s Dr Mohammed Hankir and Professor Swen Hesse talk to Oliver Hotham about how their research could dramatically change our understanding of a problem that affects more than half a billion people across the globe.

In late 2014, the website of Leipzig University published a strongly worded article discussing new research on the controversial subject of obesity. Referring to obese individuals as simply being fat, it argued, was offensive and archaic. Instead, the writers stated that the German term ‘esssucht’, which literally translates to ‘food addiction’, is perhaps not only more sensitive but, taking new research into account, also more closely reflective of what is now believed to take place in the brains of those who suffer from obesity.

“Given the current climate – where we’ve got almost ubiquitous access to these highly palatable, very energy-dense foods – understanding the hardwiring and the structural underpinnings of what drives at times compulsive feeding behaviour is very important,” argues Dr Mohammed Hankir, who, along with Professor Swen Hesse and colleagues is conducting the cutting-edge research that inspired the original article, ‘Examining the Effects of Obesity-fighting Surgery on the Brain Responses to Fatty Food’.

The concept of esssucht is central to their theory: the brain’s responses to palatable foods are comparable in many ways to what happens when we use drugs, such as amphetamine and cocaine – which can be observed with imaging technology.

Hesse and Hankir have strong backgrounds in in-vivo imaging techniques such as PET and MRI, with the former trained in clinical and the latter in preclinical research, allowing the duo to perform complementary investigations on the subject.

“I used imaging techniques during my doctoral training,” explains Hankir. “I was in a lab that was developing novel hormone-based treatments for obesity, and I have just continued on from that research. At the time, we were looking more at what’s called the homeostatic regulation of body weight. Now, I’ve progressed from there onto examining the issue from the hedonic or pleasurable side.

“Simply stated, homeostatic feeding can be viewed as feeding because you need to, whereas hedonic feeding is feeding because you want to. Basically, that’s a major distinction we want to examine – when you’re eating because you like it, regardless of the negative consequences.

“Remarkably, it seems that it is not the flavour of sweet and fatty foods, but rather their sheer high caloric value that makes you feel good and drives habit formation,” adds Hankir.

The study of obesity is undoubtedly coloured by social and cultural attitudes toward the overweight,
with many – despite obvious causal links between obesity, poverty and mental health issues – keen to label the obese as merely lazy, or lacking the self-discipline to get fit and improve their lives.

Hesse and Hankir’s research, however, could conclude something quite different: that overeating and high- sugar/fat foods can get us hooked by permanently changing how our brains respond to them, leaving us dissatisfied with food that does not give us the same kick.

“Some people could be genetically predisposed to have different brain-functional responses to, for example, consumption of a high-fat food such as chocolate milkshake,” says Hankir.

In some ways, Leipzig’s researchers are attempting to prove that what neuroscientists know to be true for drug addicts also rings true in obesity.

“That’s the question on everybody’s lips at the moment,” they say. “Why almost exactly the same anatomical regions, the exact same neurotransmitters, are involved.

“The answer is that it’s pretty much a combination of numerous different factors – the environment, our genetics, our willpower, the psychological element – and these might vary from one individual to another. It’s very topical at the moment, this whole idea of addiction to food.”

Hankir’s recent work centres on examining the consequences of what is believed by many to be the only cure for morbid obesity: gastric bypass surgery. The operation works by dramatically decreasing excess weight, by 65–80%, and curtailing the patient’s desire to consume fatty food – in other words, rendering them unable to excessively eat.

“It is well known that after a patient has had gastric bypass surgery, they show a profound change in their eating habits,” explains Hankir. “Craving for high-sugar and high-fat food subsides, and patients begin to switch their preferences to healthier alternatives.”

To investigate this phenomenon in more detail, researchers took samples from the brains of rats before and after the gastric bypass procedure, and observed a fundamental change in the neural response to eating high- fat food.

In short, gastric bypass surgery works because it not only physically restricts the body from overeating but also ‘cures’ the patient of their esssucht. The research is working in stages, examining the response of a range of different hormone and neurotransmitter systems.

“We essentially looked at the changes in the brain after that surgery to find out how this could be driving changes in behaviour and feeding patterns, ultimately leading to long-term weight loss,” says Hankir. “At the

moment, we are looking at changes in dopamine, a very similar neurotransmitter to serotonin, and our pilot studies would suggest that there are indeed changes in dopamine signalling in discrete areas of the brain in our model.

“The surgery works because it is also targeting the reward centre in the brain,” he argues. “I would say there’s a lot to be learnt from how surgery affects the brain, and in particular the serotonergic and dopaminergic pathways.”

The nature of Hankir’s experiments allows his team to perform direct quantitative analysis of any changes in dopamine signalling. These findings will then be translated into human imaging studies headed by Hesse, who will look at morphological and molecular changes in the brain, and how they are associated with changes in bodyweight and various other indices.

This type of translational research is rare, and Leipzig provides one of the few environments in the world with dedicated PET/MRI systems for preclinical and clinical studies backed by a federally funded initiative, which pours millions of euros into obesity research at the Integrated Research and Treatment Centre for Adiposity Diseases, as it is known.

“What you can do is make associations between a certain type of genetic or epigenetic modification, and how that relates to changes in brain structure and function,” says Hesse. “Essentially, we’re examining obesity at the molecular, neural and behavioural levels.”

In showing the effects gastric bypass surgery has on the brain, Hankir says they also hope to encourage the idea that it should be seen as a ‘cure’ for obesity, in a general and neurological sense.

The research remains incomplete, of course, and Hankir and Hesse are understandably reluctant to say that anything is conclusive just yet, but they are optimistic and are keen to discuss ideas about how their work, when finished, could translate into helping to treat obesity.

“We’re at the early stages,” says Hankir. “If we were to make a finding that there are changes in dopamine after surgery in human patients, then we’d be a long way from producing a drug that would be used as a treatment for obesity. But we’re getting information that’s never been obtained before, so this is all very exciting.”

If obesity is comparable to drug addiction, the implications for medical care – beyond gastric bypass surgery – are that it should begin to be treated as such, from the development and introduction of preventative programmes to rehabilitative measures for those who suffer from it.

“It all comes back to prevention,” argues Hankir. “Once you’ve been exposed to a reward like high-fat or high-sugar food, your brain almost irreversibly changes – in its structure and the way that it signals – and so, dare I say, you’ve got a permanently diseased brain.

“We know that for somebody who’s exposed to, say, a drug at an early stage, that will have more of an effect on brain structure and function than at a later stage. So for mothers who are obese during pregnancy, for example, that trait can be transmitted to their offspring in a similar way.”

Hesse argues that an important way of treating suffering patients could be the use of cognitive behavioural therapy (CBT), a psychotherapy approach that seeks to target and eliminate the negative thought patterns that can lead to depression and anxiety.

Much like gastric bypass surgery, neuroimaging is increasingly being used to demonstrate that CBT works because it can rewire responses in the brain, restoring stability to troubled minds. This could provide a respite, along with as-yet-unclear drug treatments, for those suffering from compulsive overeating, Hesse believes.

The study of obesity is changing. What has often been believed to be a condition caused by poor self-control and psychological issues is now considered to be much more likely due, at least partially, to a rewiring of the brain’s relationship with pleasure – the serotonin and dopamine neurotransmitter signalling.

For the millions who suffer from what is rapidly becoming one of the great public health questions of our time, this new research, and the treatments it may lead to, could make all the difference.

Photocredit: Wikimedia commons

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