Continuing in my miniseries on reasons why obesity should be considered a disease, I turn to the idea that obesity is largely driven by biology (in which I include psychology, which is also ultimately biology).
This is something people dealing with mental illness discovered a long time ago – depression is “molecules in your brain” – well, so is obesity!
Let me explain.
Humans throughout evolutionary history, like all living creatures, were faced with a dilemma, namely to deal with wide variations in food availability over time (feast vs. famine).
Biologically, this means that they were driven in times of plenty to take up and store as many calories as they could in preparation for bad times – this is how our ancestors survived to this day.
While finding and eating food during times of plenty does not require much work or motivation, finding food during times of famine requires us to go to almost any length and risks to find food. This risk-taking behaviour is biologically ensured by tightly linking food intake to the hedonic reward system, which provides the strong intrinsic motivator to put in the work required to find foods and consume them beyond our immediate needs.
Indeed, it is this link between food and pleasure that explains why we would go to such lengths to further enhance the reward from food by converting raw ingredients into often complex dishes involving hours of toiling in the kitchen. Human culinary creativity knows no limits – all in the service of enhancing pleasure.
Thus, our bodies are perfectly geared towards these activities. When we don’t eat, a complex and powerful neurohormonal response takes over (aka hunger), till the urge becomes overwhelming and forces us to still our appetites by seeking, preparing and consuming foods – the hungrier we get, the more we seek and prepare foods to deliver even greater hedonic reward (fat, sugar, salt, spices).
The tight biological link between eating and the reward system also explains why we so often eat in response to emotions – anxiety, depression, boredom, happiness, fear, loneliness, stress, can all make us eat.
But eating is also engrained into our social behaviour (again largely driven by biology) – as we bond to our mothers through food, we bond to others through eating. Thus, eating has been part of virtually every celebration and social gathering for as long as anyone can remember. Food is celebration, bonding, culture, and identity – all features, the capacity for which, is deeply engrained into our biology.
In fact, our own biology perfectly explains why we have gone to such lengths to create the very environment that we currently live in. Our biology (paired with our species’ limitless creativity and ingenuity) has driven us to conquer famine (at least in most parts of the world) by creating an environment awash in highly palatable foods, nutrient content (and health) be damned!
Thus, even without delving any deeper into the complex genetics, epigenetics, or neuroendocrine biology of eating behaviours, it is not hard to understand why much of today’s obesity epidemic is simply the result of our natural behaviours (biology) acting in an unnatural environment.
So if most of obesity is the result of “normal” biology, how does obesity become a disease?
Because, even “normal” biology becomes a disease, when it affects health.
There are many instances of this.
For example, in the same manner that the biological system responsible for our eating behaviour and energy balance responds to an “abnormal” food environment by promoting excessive weight gain to the point that it can negatively affect our health, other biological systems respond to abnormal environmental cues to affect their respective organ systems to produce illnesses.
Our immune systems designed to differentiate between “good” and “bad”, when underexposed to “good” at critical times in our development (thanks to our modern environments), treat it as “bad”, thereby creating debilitating and even fatal allergic responses to otherwise “harmless” substances like peanuts or strawberries.
Our “normal” glucose homeostasis system, when faced with insulin resistance (resulting from increasingly sedentary life circumstances), provoke hyperinsulinemia with ultimate failure of the beta-cell, resulting in diabetes.
Similarly, our “normal” biological responses to lack of sleep or constant stress, result in a wide range of mental and physical illnesses.
Our “normal” biological responses to drugs and alcohol can result in chronic drug and alcohol addiction.
Our “normal” biological response to cancerogenous substances (including sunlight) can result in cancers.
The list goes on.
Obviously, not everyone responds to the same environment in the same manner – thanks to biological variability (another important reason why our ancestors have made it through the ages).
But, you may argue, if obesity is largely the result of “normal” biology responding to an “abnormal” environment, then isn’t it really the environment that is causing the disease?
That may well be the case, but it doesn’t matter for the definition of disease. Many diseases are the result for the environment interacting with biology and yes, changing the environment could indeed be the best treatment (or even cure) for that disease.
Thus, even if pollution causes asthma and the ultimate “cure” for asthma is to rid the air of pollutants, asthma, while it exists, is still a disease for the person who has it.
All that counts is whether or not the biological condition at hand is affecting your health or not.
The only reason I bring up biology at all, is to counter the argument that obesity is simply stupid people making poor “choices” – one you consider the biology, nothing about obesity is “simple”.
While much has been written on how the current obesity epidemic is not limited to humans but also includes house hold pets and zoo animals, some species appear to be more obesity prone than others.
Among dogs, which for centuries have been selectively bred to transform the wild type into all shapes, sizes and temperaments, some breeds likewise appear more prone to weight gain than others – these include labrador retrievers.
Now, a study by Eleanor Raffan and colleagues from Cambridge University, UK, in a paper published in Cell Metabolism, have identified a common deletion within the POMC gene that enhances appetite and feeding behaviour.
The 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12% disrupts the β-MSH and β-endorphin coding sequences and is associated with body weight (mean effect size 1.90 kg per deletion allele, equivalent to 0.33 SDs), adiposity, and greater food motivation.
Among another 39 dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation.
The influence of this mutation on feeding behaviour is likely complex:
“It has been reported that owners of more highly food-motivated dogs make greater efforts to limit their dogs’ access to food. However, there is evidence to suggest dogs are able to influence both the type and quantity of food offered to them by their owners. It is possible that behavior changes related to the mutation are sufficient to lead to increased food intake (either by scavenging or soliciting owner-provided food).”
Interestingly, the mutation was found to be significantly more common in Labrador retrievers that had been selected to become assistance dogs than pets suggesting that there may be something about this deletion that positively influences temperament, making them best suited for this kind of work.
“Temperament and “trainability” are the main drivers for selection of assistance dogs, and “positive reinforcement” with food reward is a mainstay of puppy training. We therefore hypothesize that dogs carrying the POMC deletion may be more likely to be selected as assistance dogs.”
Overall, and this should come as no surprise, these findings show that mutations in the same system that regulates human weight and appetite (and perhaps temperament?) is found in obesity prone canines.
Which, incidentally, brings up the issue of selective breeding in humans – but that’s another story.
As this year’s Congress President, together with World Obesity Federation President Dr. Walmir Coutinho, it will be our pleasure to welcome delegates from around the world to what I am certain will be a most exciting and memorable event in one of the world’s most beautiful and livable cities.
The program committee, under the excellent leadership of Dr. Paul Trayhurn, has assembled a broad and stimulating program featuring the latest in obesity research ranging from basic science to prevention and management.
I can also attest to the fact that the committed staff both at the World Obesity Federation and the Canadian Obesity Network have put in countless hours to ensure that delegates have a smooth and stimulating conference.
The scientific program is divided into six tracks:
Track 1: From genes to cells
- For example: genetics, metagenomics, epigenetics, regulation of mRNA and non–coding RNA, inflammation, lipids, mitochondria and cellular organelles, stem cells, signal transduction, white, brite and brown adipocytes
Track 2: From cells to integrative biology
- For example: neurobiology, appetite and feeding, energy balance, thermogenesis, inflammation and immunity, adipokines, hormones, circadian rhythms, crosstalk, nutrient sensing, signal transduction, tissue plasticity, fetal programming, metabolism, gut microbiome
Track 3: Determinants, assessments and consequences
- For example: assessment and measurement issues, nutrition, physical activity, modifiable risk behaviours, sleep, DoHAD, gut microbiome, Healthy obese, gender differences, biomarkers, body composition, fat distribution, diabetes, cancer, NAFLD, OSA, cardiovascular disease, osteoarthritis, mental health, stigma
Track 4: Clinical management
- For example: diet, exercise, behaviour therapies, psychology, sleep, VLEDs, pharmacotherapy, multidisciplinary therapy, bariatric surgery, new devices, e-technology, biomarkers, cost effectiveness, health services delivery, equity, personalised medicine
Track 5: Populations and population health
- For example: equity, pre natal and early nutrition, epidemiology, inequalities, marketing, workplace, school, role of industry, social determinants, population assessments, regional and ethnic differences, built environment, food environment, economics
Track 6: Actions, interventions and policies
- For example: health promotion, primary prevention, interventions in different settings, health systems and services, e-technology, marketing, economics (pricing, taxation, distribution, subsidy), environmental issues, government actions, stakeholder and industry issues, ethical issues
I look forward to welcoming my friends and colleagues from around the world to what will be a very busy couple of days.
For more information on the International Congress on Obesity click here
For more information on the World Obesity Federation click here
For more information on the Canadian Obesity Network click here
This is once again demonstrated in a fascinating series of experiments by Stefano Guidotti and colleagues from the University of Groningen, The Netherlands, in a paper published in Physiology and Behaviour.
The researchers performed their experiments in mice that were selectively bred over 50 generations to voluntarily spend hours in running wheels. Interestingly, the female “runner” mice remain resistant to becoming obese as adults when exposed to a high-fat diet even when they don’t have access to a running wheel.
Thus, these mice are resistant to developing obesity whether they run or just sit around.
What the researchers now show is that this “resistance” to gaining excess weight (bred over generations) can be fully cancelled out simply by exposing the mice to a high-fat diet for a couple of days shortly after birth.
With this exposure, these mice (and even their offspring) are suddenly no longer resistant to weight gain later in life and in fact gain as much weight on high-calories diets as normal mice.
Even more interestingly, the short term perinatal exposure to the high-energy diet does not cancel out their love for running. When given a wheel, they continue running just as much as before but even this no longer prevents them from gaining weight.
Thus it appears that exposure to a high-energy diet during the perinatal period can have profound effects on the risk of developing adult obesity even in animals bred to be obesity resistant – and, the love for running, does not appear to protect against weight gain.
Or, as the authors put it,
“..resistance to high-energy diet-induce obesity in adult female mice from lines selectively bred over ~ 50 generations for increased wheel running behavior was blocked by additional perinatal high-energy diet exposure in only one cycle of breeding. An explanation for this effect is that potential allelic variants underlying the trait of diet-induced obesity proneness were not eliminated but rather silenced by the selection protocol, and switched on again by perinatal high-energy diet exposure by epigenetic mechanisms”
Moreover, this effect of perinatal high-energy diet exposure and its “reversal effect” on obesity resistance can be passed on to the next generation.
Reason enough to wonder just how much the rather dramatic changes in perinatal feeding of infants over the last few decades may be contributing to the obesity epidemic.
Shortly after a meal, there is a spike in the cerebrospinal fluid concentration of nutrients with direct access to various nutrient-sensitive sites in the brain.
Now a paper by Olof Lagerlöf and colleagues, published in SCIENCE, shows that in mice, the glycosylation enzyme O-GlcNAc transferase (OGT), present in a wide range of neurons involved in energy regulation and feeding behaviours, may play an important role in the satiety response.
Genetic and molecular manipulation of this enzyme in adult mice resulted in marked effects on feeding and weight gain.
Reducing the activity of the enzyme resulted in animals eating much larger meals (but not more often) with substantial gain in fat (but not lean) mass.
In contrast, increasing the activity of this enzyme resulted in reduced food intake during eating episodes.
Not only does it make sense that a molecule known to play a role as a nutrient-sensor would play a role in the central regulation of food intake, but the authors are optimistic that this enzyme may be a target for finding new anti-obesity medications.