Obesity – The brain is the battleground

Obesity can seem fairly straightforward to explain – if we consume more calories than we need, we pile on the pounds. But in fact, the problem is much more complex. It seems our bodies are hard-wired to hang on to those extra calories, probably because for thousands of years, it was a basic survival mechanism. 


By Mads Tang-Christensen  |  Published 11 October 2018


 

Going back to the Stone Age, natural selection favoured those of us whose bodies did a good job of storing energy reserves in times of feast, and drawing on those reserves in times of famine. That’s how we’ve evolved.

But in today’s world, many of us have easy access to too much tasty food and drink, and lead relatively sedentary lives. So, when you combine a natural predisposition to store calories as fat, together with an environment that makes it easy to over-consume calories, it’s not surprising we face an obesity epidemic of global proportions. Our fundamental genetic make-up may not change much from generation to generation, but our lifestyles influence how our genes are expressed into physical characteristics, like a tendency to gain weight.

 

The relationship between our brain and obesity

The brain is the battleground where nature’s tendency to hang on to calories fights with our attempts to maintain a healthy weight. Basically, to understand obesity, we really must understand what’s going on in our brains. For example, look at the GLP-1 molecule, a peptide that plays a key role in blood sugar regulation. People may know that there are GLP-1 receptors in the pancreas that help to release insulin, but they may not realize that there are also GLP-1 receptors in the brain. These receptors aren’t involved in insulin release, but they do play a key role in how our bodies regulate weight because they help to stimulate that sensation of feeling full after eating. This is one example of that tight link between obesity and type 2 diabetes, which is why obesity is a natural area for Novo Nordisk scientists to work on.  

 

Searching for the ’holy grail’      

In obesity research, we are searching for the ‘holy grail’ in body weight regulation by trying to understand the mechanism that the body uses to keep us at a certain weight, a sort of ‘set-point’ or “settling point”. Why is it, for example, that a person may be able to lose weight, but within a few weeks, the weight creeps back up to where it was, even though their calorie intake hasn’t increased? In fact, in some cases, a person can put the weight back on even while consuming fewer calories than before.

It’s as though there were some internal drive to get back to that starting weight, a sort of switch that tweaks a person’s energy expenditure until they’ve regained the kilos they had lost in dieting. There’s been a lot of research over the years into this phenomenon by a number of scientists. At Novo Nordisk we’re trying to pin-point where exactly in the brain such a switch could be located, and we’re exploring whether it’s something we could address with a medicine. If it is, then you could imagine that one day, we might be able to help people with obesity to ‘reset’ their weight to a new, healthier starting point. For me, that’s a sort of scientific light-house, it’s what my team and I are working towards, because if we’re successful, we could help millions of people living with obesity.

 

Obesity is not a self-inflicted disease

My hope, in addition to the scientific advances we are making, is that more people will better understand just how complex obesity is.  People living with obesity are struggling to lose weight. But a complex system in our bodies is working against them. A lack of understanding has led to unhelpful, and hurtful myths.

For example, there’s a widespread view that obesity isn’t a disease and that gaining weight is a matter of individual choice. I think that drives a lot of stigma.  And I really reject that notion that obesity is a self-inflicted disease. Obesity sits at the core of most metabolic diseases, like type 2 diabetes or NASH (non-alcoholic steatohepatitis). It’s simply not the case that some diseases are more ‘real’ than others.

If we’re going to address the problem of obesity across the population, we must realize that this is a medical condition that we need to treat. Obviously, like with many diseases, there are lots of things that the individual can do, to try to live healthily and to exercise. But the bottom line is that one wouldn’t argue with a patient suffering with type 2 diabetes that it was their own fault, and neither should we with obese patients.  

 

The quest of a lifetime

When I was 26, and just starting out on what turned out to be a lifetime of studying the GLP-1 molecule, I really thought we’d have a solution by now. But the older I get, the humbler I’ve become. The mechanism behind the brain’s role in obesity is so elusive, it’s really the perfect quest for a researcher. And I suppose I feel a sense of awe at the mystery of it all. Fundamentally, our research is about energy intake, preserving energy and staying alive. We’re examining what’s at the core of living, and that’s what makes it a real joy for me to go to work every day. 

 

For more information, contact Scott Dille.

 

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