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The SCIENCE

The science of obesity is moving at an incredible pace. Every day, new research on obesity is published from multiple areas of the scientific community. More information than ever points towards obesity as being a chronic, relapsing, biologically and environmentally driven disease that is not within the control of the individual.

Brain chemistry and signalling, genetics, epigenetics, and the environment all have a part to play, according to emerging research.

Scroll down to learn about some of the internal body mechanisms that may contribute to this complex disease and how research projects like SOPHIA focus on personalised treatments for patients.

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Prof Bart Van der Scheuren MD, PhD: The Science of Obesity

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Transcript

I think in the past 10 to 20 years we have learned an enormous amount about the exact mechanism that underlies the pathogenesis of obesity. We have learned that our food intake, but as well our metabolism, is very closely monitored by a very complicated system of hormonal and neuronal influences, which will always try to keep your weight stable. And so this explains actually why the human being is able to defend its body weight.

By understanding the exact hormonal circuits, we’ve also been able to intervene in them. One of the very important hormones is leptin. It’s a hormone that is produced by our fat tissue to really give an insight to the brain, to the hypothalamus in the brain, on how the status of energy storage in the form of fat currently is in our body.

What we have realized is that people who are living with obesity become resistant to this signal, and so their hypothalamus, their brains, don’t hear anymore, have no exact way of knowing what the fat storage at each given moment is. And this apparently is fundamental in obesity further developing. On the other hand, we have also learned that there are hormones in the gastrointestinal system that will immediately also give signals to the brain, and the hypothalamus is really kind of the orchestra leader, if you want.

It kind of tightly regulates our temperature, but also our metabolisms, our food intake, our hunger, our satiety. And these hormones, they can now be produced as drugs, and so we are in the capacity of intervening in this very close-knit hormonal system, and trying to get the balance again to a lower weight, in other words, shed the extra kilos that are on board, because something went wrong in that homeostasis, in that equilibrium. So, I think that’s where the biggest progress has been made.

The biggest progress is an understanding of how the body regulates its weight, and through that understanding, being able to intervene in the mechanisms that lead to our weight being stable.

The Weight Set Point/Set Range Theory

When the body functions optimally, it tends to maintain a stable weight within a limited range. It does this via internal biological systems and without conscious control from the individual. This set point (or narrow range) is what the body deems to be safest for its survival, and it will resist deviations away from this using mechanisms including hormone signalling and brain chemistry.

In individuals with obesity, the complex interplay of hormones, neurotransmitters, and cellular signalling pathways involved in regulating energy balance becomes disrupted. This dysfunction leads to a fluctuating weight set point, making it significantly more challenging to maintain a healthy weight. Essentially, the body’s ‘thermostat’ is set too high and constantly works to maintain a weight that is ultimately detrimental to health.

Weight set point dysregulation is a significant feature of obesity disease.

It’s important to note that while weight set point dysregulation is a significant factor in obesity, it is not the only factor. External factors, as well as biological factors, are continually influencing each other.

Many things can affect the set point including certain illnesses, stress, certain pharmaceuticals or medicines and bariatric surgery.

For more information, see:

Dr Andrew JENKINSON: The Weight set point

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Transcript

So people’s weight is not randomly determined by how much they like food or how greedy they are or how lazy they are is determined by your individual weight set points. And this is calculated by the weight control center in your brain. The hypothalamus, depending on your genes, but also depending on various other parts of the environment, including what type of food you eat and whether you have a lot of stress and whether you sleep well.

So the elements in the foods that are important include, you know, if you have too much refined carbohydrates and sugar, that’s going to increase your insulin level, which is going to block the weight control hormone, leptin. This is going to put your weight set, point up, other factors such as high stress can increase your cortisol, lack of sleep can increase cortisol, and these things again increase your weight set point.

So to lose weight and sustain weight loss, you need to understand why your weight is set to a high level if you’re living with obesity. And then once you understand that you can change those factors within your environment that are causing that. So you can change, you can go away from foods that are causing havoc with your metabolism, and you can, you know, try and de-stress and sleep better

Metabolic Adaptation

Metabolic adaptation may be described as a process of energy conservation that occurs in the body, often as a response to calorie restriction.

This adaptive process is crucial for survival in times of food scarcity, as it ensures that the body doesn’t expend more energy than it can acquire.

  • The body lowers the basal energy rate, which it uses while resting.
  • It becomes more efficient at absorbing and storing energy.
  • It adjusts hormone levels to achieve these goals.

Metabolic Adaptation, coupled with dysregulation of the weight set point, triggers mechanisms to conserve energy and minimise the rate at which calories are burned via hormonal changes and body temperature regulation. This all occurs outside of conscious control. In the presence of obesity disease, this makes it highly challenging to positively affect weight or weight-related complications without specialist support.

Further reading on this subject

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Leptin Resistance

Leptin is a hormone produced by adipose tissue cells (also known as fat cells) that acts like a messenger from the body to the brain. It communicates how much energy the body has in storage and helps regulate appetite, energy expenditure, and the rate at which the body burns that energy.

When it functions optimally, the hormone leptin signals the brain to downregulate hunger and increase energy expenditure to maintain healthy body weight. However, in people living with obesity, the leptin signal can become “blocked” or “not seen” by the brain. This is called leptin resistance. Several things can contribute to leptin resistance over time, including inflammation, high insulin or insulin resistance, and genetic predisposition. When leptin resistance occurs, the brain doesn’t receive a clear message from the cells that there is enough stored energy, which can lead to persistent hunger and a lower metabolic rate.

Leptin resistance, dysregulation of the weight set range, and maladaptive metabolic responses can all combine, meaning specialist support is essential for the health of the individual with obesity disease.

For more information, see:

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ULTRA PROCESSED FOOD

Energy Intake, our Modern Food Environment and Ultra Processed Foods.

Our modern food environment, and particularly ultra-processed foods (UPFs) are increasingly being linked to rising levels of obesity.

What are ultra-processed foods (UPFs)?

UPFs come in many forms and are widely found in our modern food environment. Ways to spot them include long lists of ingredients that wouldn’t be used in a domestic kitchen or a long shelf-life.

It is important to note:

  • Not all UPFs are created equal: Some UPFs may be healthier than others depending on their ingredients and overall nutritional profile.
  • Other factors play a role: UPF consumption is just one factor contributing to obesity, and additional factors such as individual biology, genetics, and overall dietary patterns also play important roles.

Why are UPFs a concern?

  • They are created to be highly palatable: UPFs are often engineered to be extremely tasty and addictive, using flavourings, textures, and macronutrient combinations that trigger the reward centres in the brain.
  • This “hyper-palatability” can interact with our ancient evolutionary appetite and motivation systems to generate over-consumption.
  • They are often packaged with misleading health claims or portion sizes.
  • Research, investigating the specific mechanisms by which UPFs influence energy intake, includes effects on appetite hormones, gut bacteria, and reward pathways, is a relatively recent area of study.
  • The long-term effects of these foods on people more prone to obesity (via their specific genetic makeup) are not yet known.
  • The body has metabolic and hedonic regulatory systems for maintaining our weight “set-point” and overexposure to UPFs can override these systems’ homeostasis (balance).

The latest science

Among some of the latest peer-reviewed scientific research that suggests a link between the consumption of ultra-processed foods and obesity are:

A systematic review in the Nutrition Journal analysed 20 epidemiological studies on the health outcomes associated with ultra-processed food consumption. This review included over 334,000 participants and found a significant association between the consumption of ultra-processed foods and an increased risk of overweight and obesity, among other health outcomes​​.

Research published in the European Journal of Clinical Nutrition also supports the link between ultra-processed food consumption and obesity. This includes studies conducted in Iran, Canada, Brazil, the United States, and several European countries, which have consistently demonstrated a strong association between high consumption of ultra-processed foods and increased obesity indicators​​.

For more information, see:

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EMERGING SCIENCE

Project SOPHIA

SOPHIA (Stratification of Obese Phenotypes to Optimize Future Obesity Therapy) is a €16 million EU and industry-supported international research project to develop usable tools to predict who will develop complications of obesity.

Obesity is associated with more than 200 complications, but we cannot yet predict who will develop them or be affected. Moreover, there are no predictors for who will respond to obesity treatments.

SOPHIA will identify and characterise clinically-meaningful subpopulations of patients with obesity ensuring the use of the right treatment for the right people at the right time. The research consortium will use this knowledge to provide a model for how the world talks about obesity, focused on new understandings and a new vocabulary.

The voices of people living with obesity are at the heart of SOPHIA through a Patient Advisory Board, ensuring that patients’ insights, opinions and wishes are comprehensively included in the study. The research group will contribute to a more patient-centric and equitable narrative around obesity and its multiple impacts on individuals from both a social and medical perspective. It all starts with obesity being a chronic disease, not something people choose to live with.

The end date of the study is May 2025

Project SOPHIA Factsheet (https://www.imi.europa.eu/projects-results/project-factsheets/sophia)
Project website (https://imisophia.eu)

Project SOPHIA Logo

“Obesity Care and Weight Loss are not the same.”

 
International Obesity Collaborative

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