The Complex Causes of Obesity

While the history of research into obesity and related health problems has had opposing camps for over a century, one camp came to dominate our widely held assumptions about what makes us fat. The simple and appealing concept that eating more than we use makes us fat has a grip on society and has done a great deal of damage. This so called ‘energy-balance disorder’ has led to the stereotype that fat people are weak and gluttonous but growing evidence suggests this is often unfair and a gross over-simplification. This demonisation of ‘fat’ has spawned, and been reinforced by, modern image (glossy magazines) and health empires (gyms and diet fads) where skinny and toned is worshipped at great profit to some but little benefit to most. There have been many studies in the past that have cast doubt on the simple energy-balance model and, with modern advances in genetics, neuroscience and even our increasing appreciation of the role our gut microbiome plays, more studies are backing them up. The alternate, and more complex, model for obesity points the finger at specific physiological malfunctions in individuals either due to congenital curses (genetically linked) or through a combination of diet and lifestyle with the energy-balance concept relegated to a potential exacerbator. While these explanations may appear to exonerate the overweight of responsibility, I think they should rather be viewed as a path to empowerment to effectively tackle any health problems and are likely to be incorporated by the growing field of personalised medicine.

    So first off, we need to get a rough overview of how the energy-balance model works. The concept is simple in that excess energy, in the form of calories, is stored by the body in fat cells. Thus, over time an excess of eating and a dearth of exercise will cause our fat cells to grow and multiply. It is worth pointing out that I'm not saying this process is irrelevant to the issue of obesity (it certainly doesn't help) but I will argue we've had the emphasis wrong. The power of this model is in its simplicity which has been preyed on by diet fad after diet fad, fitness gurus and even purveyors of sugary goods (‘to be enjoyed as part of a healthy/active lifestyle’!). A common associated mantra is ‘a calorie is a calorie’, which is again unhelpful, most clearly seen in the case of sugar. The alternate models try to explain the process that leads to this fat storage and how this process varies between individuals due to genetics and lifestyle. While uncomfortable as a scientist I will stray into the anecdotal to highlight a point. I am clinically underweight and have been my whole life and while I probably exercise more than the average Briton (not hard really) I certainly don’t watch my calories and usually eat three full meals a day and enjoy my calorific beer (full of alcohol and complex carbohydrates). In short, the calories just don’t stick to me and as far as I am concerned I cannot put weight on, and trust me I have tried. On the other hand, I have a number of friends who will quite normally gain (and then lose) 5kg over the festive period, prime candidates for those new years resolutions and gym memberships. The point is that there is wide variation in how people respond to their food and clearly the energy-balance model is limited at best. So why the differences? Well without going into huge detail I’d like to highlight some key examples that might well explain these differences.

    Hormones: Many studies have pointed the finger at hormone imbalances as a cause for obesity and most other factors can be thought of as feeding into and affecting these mechanisms. There are many different hormones that influence both the rate of fat deposition and general metabolism. It’s important to also remember that hormones mediate interactions between our brain and our body and this goes both ways. In fact, the ordering of this cause and effect has been suggested to mean that ‘we eat more because we are getting fat’  which is why I said earlier that energy-balance issues are relegated as secondary issues. The two key hormones in this are insulin and leptin. Insulin is released when we have sugar in the blood and it instructs various tissues to extract this sugar and store it as glycogen and, importantly, fat to be used as energy stores when needed. Type 2 diabetes is a disease in which over time our bodies become more and more resistant to insulin and so we produce more and more to try have the same effect. This rise in insulin is thought to have a knock-on effect causing leptin resistance, although this is disputed by some. Leptin, produced by fat cells, is one of two hormones, along with its antagonist ghrelin, that regulates our hunger sensation and it is leptin’s job to tell our brain when we’ve had enough food. So with resistance to leptin, our brains fail to get the message that we’ve had enough, which equates to ‘we need more, I’m starving’, and so we eat more exacerbating the problem. This is a big problem as the will-power required to eat less can be immense as we fight what is effectively a starvation signal in our brain. So according to this model our diet, e.g. high sugar, leads to fat deposition and hormonal resistance in turn leading to a behavioural change that often reinforces the problem.

    Ghrelin is another interesting example in which it can specifically go wrong in some people. Ghrelin is released by the gastrointestinal tract and relates to the size of the stomach. Normally, a full stomach means little ghrelin is released while an empty stomach induces ghrelin production. Ghrelin then acts on the same target cells in the brain as leptin but to convey hunger. Again, there is natural variation in how people produce and respond to ghrelin meaning some people habitually feel hungry and none more so than those with the genetic disorder known as ‘Prader-Willi syndrome’. These people have constantly high ghrelin levels and an insatiable appetite leading to morbid obesity alongside a suite of other mental and physiological problems. In fact, one treatment for obesity is the gastric bypass in which the stomach is effectively reduced and this means that less ghrelin is produced and so hunger is reduced. It is not hard to imagine that an unfortunate combination of these hormonal problems could lead to people having uncontrolled hunger and fat deposition.

    Diet: As alluded to above, sugar has come under the spotlight for its contribution to obesity and diabetes and one of its key modes of action appears to be through how it affects insulin and leptin. Some of the most effective diets are the ‘low-carb’ diets and while they seem to work in a number of ways, their effect on the hormonal model discussed above is likely a factor. Low carbohydrate diets effectively reduce our insulin levels and so we avoid the insulin spikes and associated leptin resistance helping us eat less. Tantalising studies have shown that, at least in the short term, a diet in which carbohydrates are swapped for fats (with their own associated health problems) can result in weight loss so watch this space as more evidence comes out! The key thing here is that it does not result from a calorie reduction but a food group swap. When fat itself was demonised a few decades ago as the leading cause of obesity, we saw people and food manufacturers avoiding it while carbohydrates and especially sugars came to fill the calorie gap. This change, more so than an increasingly sedentary life, is thought to have been a key driver in the world obesity epidemic. In view of the flaws in the calorie-balance model, exercise should be viewed as a way to keep people generally healthy, but not to lose weight. Just by way of example, if I wanted to burn off the calories from a big mac (563), I’d need to jog for an hour and a half. If I just did nothing and relied upon my resting metabolic rate at 1809 calories per day, I’d need to eat three big macs a day to sustain myself. The point is we burn a pretty large amount just by living and breathing but when we need to burn the extra on top of that we need to spend a lot of time to burn seemingly little more. Keeping active helps but is unlikely to solve a weight problem if we are putting in the wrong type of food and hoarding fat.

    Gut microbiome: A third area relating to obesity is the gut microbiome. This incredibly complex ecosystem feeds on what we eat and is even thought to interact with our brains. Studies in rodents have suggested that the whole hormonal story outlined above could also be influenced by our gut bacteria. The break down of fat by bacteria is thought to result in acetate which sends signals to our brain and instructs both ghrelin and insulin to be produced! The implication is that certain gut microbiomes produce more acetate so making this effect stronger. I.e. the make up of our gut bacteria can make certain people susceptible to becoming obese through behavioural and physiological changes. The variation in peoples gut bacteria has attracted much interest recently and studies are finding correlations between certain compositions and health. Such progress has even spawned companies offering to study your microbiome and give you insights into how to best manage general health. As we understand more, the concept could allow certain treatments and preventative measures specifically targeting our guts and what grows there. We gain our mothers bacteria first and then build up our own unique ecosystem as we grow and this is then modulated by our diet through life offering different stages to target.

    So obesity could be traced back to the bacteria we inherited, acquired and encouraged through our diet with it effecting our behaviour but it goes further than this. A fantastic twin study has found for example that the obese (human) twin had a less complex microbiome, likely due to lifestyle and diet choices, while the leaner twins had a richer mixture higher in plant fibre and starch digesting bacteria. Now, while the chicken and the egg debate might erupt, the same study then used mice to demonstrate that the microbiome does have a clear effect on obesity. Sterile twin mice were populated by the bacteria from either the obese or the lean human twin. Following an identical diet, the twin mouse with the obese humans gut bacteria got fat and the other remained lean! This final example is I think very telling, especially in my personal case, as even when the calorific intake was the same, one twin got fat and the other didn’t meaning their bodies did not treat the calories the same. In one, the food went straight into fat storage while it seemed to vanish in the other.

     It appears that due to various factors there are big variations between people in how certain food is digested and absorbed, how it is stored, how it is used and how much of it we feel we need. I look forward to a time, quite soon I hope, when those struggling with obesity, or in my case being underweight, can understand why and make the appropriate targeted changes needed to be actually effective as simply telling people to eat less and run more appears woefully inadequate. At the dawn of personalised medicine, these possibilities are almost upon us and if used properly have the potential to empower all of us to get the most out of our bodies.