Why We Eat (Too Much) Page 10

  Spontaneous Combustion

  Our story of thermogenesis starts during the First World War in a draughty warehouse on the outskirts of Paris. The warehouse was a bomb-making factory and they had just discovered how to make an extra-strong type of dynamite. The lines of workers, mainly women, mixed two chemicals together – dinitrophenol (DNP) and picric acid – to make the TNT explosive, before packing it into metre-long artillery shells and soldering them shut. The work was hard and exhausting, but the supervisor noticed that his workforce was not performing as well as expected. The women complained of feeling hot and sweaty, and developing fevers, despite the lack of winter heating in the cold warehouse. After some time, it was clear that many of the women were losing a considerable amount of weight. Then disaster struck. One of the workers, a young woman in her twenties, collapsed with a raging temperature; her muscles were convulsing transiently before they turned rock-hard and stopped working. The paralysis meant she could not breathe. She died, on the factory floor, of asphyxia.

  In the 1920s, scientists from Stanford University analysed the effect of dinitrophenol (one of the chemicals used in the bomb factory) on metabolism and found that exposure to the chemical increased the resting metabolic rate by a hefty 50 per cent. Chemical, or food, energy was being converted in the muscle – not to physical energy in the form of movement, but to thermal energy in the form of heat; the side effect was that fat reserves needed to be burned to feed the energy deficit. The heat generated in the muscles raised the temperature of the body and the body compensated by sweating to cool the skin. The chemical dinitrophenol, later to be known as DNP, acted in the core of the muscle cells on the surface of the mitochondria – their cellular engines. These cellular engines normally convert fuel in the form of glucose (from our carbohydrates) to ATP (adenosine triphosphate), a molecule which acts like a micro-charged battery that cells can use for building or moving.

  Energy (glucose from food) ➞ enters cell ➞ produces ATP (cellular form of energy)

  In the presence of DNP, the engines misfire, taking in the glucose but not making ATP, and instead the fuel is converted to heat.7

  Energy (glucose) ➞ enters cell ➞ DNP blocks ATP production ➞ cell loses energy as HEAT

  Miracle Weight-Loss Cure

  By the 1930s American pharmaceutical companies had started to produce and market DNP as a revolutionary weight-loss cure. It certainly seemed to work and within a year 100,000 people had used it. However, the scientists had failed to properly assess the drug’s safety and it soon became apparent that it caused several very unpleasant side effects. The first was early formation of cataracts, leading to blindness, and the second was severe hyperthermia (overheating of the body), which led to at least one death. The drug was quickly withdrawn from the market.

  DNP made another fleeting appearance in the freezing trenches of the Russian army during the Second World War. Russian scientists modified and weakened DNP and fed it to their troops. It worked – their bodies were miraculously warmed and the rates of hypothermia dropped. The soldiers felt more comfortable, but as their treatment continued they noticed that they were also losing too much weight. Again, the drug was stopped.

  More recently DNP has started to make a comeback. Despite its clearly lethal dangers, many bodybuilders continue to use it to lose fat rapidly. It is easy to find and order online. In 2018, four people in the UK died from an overdose and the spontaneous combustion of the muscles that it causes. The final throes of death come when the muscle cells have run out of energy and cannot stop calcium flooding into them, followed by a brief fit and then a rigor mortis-like rigidity of the muscles before death occurs.

  The Search for Our Natural Energy-Burner

  Knowing the power of DNP to literally burn through our stored (fat) energy, scientists have for decades been striving to find its natural equivalent within our bodies. If a DNP-like fat-burner could be discovered, and somehow safely harnessed, this could lead to a very lucrative weight-loss drug.

  Their search began by analysing how ‘brown fat’ works. Brown fat is abundant in small animals (like mice), which need to keep warm. Unlike white fat (which stores energy), brown fat contains a protein called UTP-1 which, just like DNP, will take food energy and convert it into heat. Unfortunately, adult human bodies do not contain much brown fat, certainly not enough to be able to burn off much excess energy. So recently the search for our natural energy-burner has switched from brown fat to our muscles. Hot-off-the-press research has shown that muscle cells contain a DNP-like substance called sarcolipin, a protein that can, when our bodies so please, burn those excess calories – not by movement or exercise, but simply by converting the calories into heat energy. This heat is then easily lost into the atmosphere. The unwanted excess energy is burned off without effort.

  If you are interested in exploring the background to thermogenesis – this fascinating method that our muscles use to burn energy and preserve our weight set-point – in more detail (maybe you are a doctor or scientist), please access the online Appendix at www.whyweeattoomuch.com.

  Summary

  Let’s recap where we are so far with the explanation of the metabolic processes regulating our weight. We have established that our energy reserves, i.e. how much fat our bodies carry, are controlled by our subconscious brain and not our conscious brain. We can try and override our subconscious brain for short periods of time, by dieting, but ultimately our negative feedback processes will draw our weight back to our own personal set-point. The weight set-point is calculated by our brain from our environment, our history and our genes. It can be altered upwards or downwards if we understand the processes involved (this will be discussed further in Part Three). If we over-eat or under-eat, and our weight goes too high or too low compared to our set-point, then our basal metabolic rates are switched upwards or downwards to restore us to our set-point weight.

  Metabolism is adjusted like a dimmer switch. If our body wants us to lose weight because it is currently higher than our set-point (for example, after Christmas), it will increase metabolic ‘burn’. We have seen compelling evidence that this burn, or metabolic adaptation to over-eating, is controlled via sympathetic nervous system activation (the system we traditionally associate with the fight or flight response). When the sympathetic nervous system becomes more active, we feel the consequences of this. Some of those consequences feel good, like clear thinking and a sense of wellbeing, but others are not so good, like higher blood pressure and glucose levels. In addition to this, SNS activation causes excess energy to be lost by switching on thermogenesis in the muscles. As a result we may feel hot and notice that we sweat easily as the body cools down to compensate for the muscular heat generation.

  When our body wants us to gain weight because our weight is currently lower than our set-point (i.e. during a diet), our metabolism can decrease dramatically, down to around 1,000kcal/day. We have seen evidence that this occurs when the parasympathetic nervous system becomes more active. This reduces energy expenditure by the heart (blood pressure becomes normal) and shuts off thermogenesis in the muscles – making us feel cold.

  Metabology Rule 1, our first law of thermodynamics (energy stored = energy in – energy out), now seems a lot more dynamic. Energy out varies dramatically – metabolism cannot be controlled by our free will. In the next chapter, we will examine the ‘energy-in’ part of the equation. Can we consciously control the amount of food, and calories, that we take in over a long period of time, or is this also under some kind of subconscious control?

  FOUR

  Why We Eat

  How Our Appetite (and Satiety) Works

  ‘I’m losing weight but I don’t feel hungry any more. Sometimes I have to set my alarm to remind myself to eat lunch.’

  This is one of the most common statements that patients make following bariatric surgery. They have tried dieting for most of their lives, but have been unsuccessful every time. They have a perception that they are weak-willed because they al
ways seem to give in to their hunger after they lose some weight on a diet. But suddenly, after bariatric surgery, the veil of guilt is lifted. Their obesity is going away and they feel in control of it. They are losing vast amounts of weight, but are not experiencing the rebound voracious appetite that they have been used to on a diet. Apart from their happiness in being able to lose weight, they are, I sense, relieved to discover that it was not their own greed letting them down. They didn’t have the character flaw or weakness that they suspected they had, and which society implied they had, after all. What they had been experiencing with diet after diet were the normal protective hunger signals generated by food restriction. As we saw in chapter 3, in just the same way that metabolism is altered drastically by weight loss, so too are the signals governing how much food that we are directed to eat by our subconscious brain. These ‘energy-in’ signals are switched off after bariatric surgery.

  One of the fantastic consequences of bariatric surgery is that it has stimulated research into appetite regulation. Pharmaceutical companies are well aware of the remarkable changes in appetite that occur after this type of surgery and they want to understand it. Once they have learned about the mechanisms, they can work to produce a drug to mimic the effect of bariatric surgery on appetite – and suddenly they will have a trillion-dollar product on their books. So lots of ongoing research is being funded.

  We saw in the previous chapter that our metabolisms are dynamic, varying in order to regulate our weight to the desired set-point. ‘Energy out’ changes constantly. But what about the ‘energy-in’ part of our energy-balance equation? How is this regulated?

  There are two signals that drive our food intake: the signal to start eating and the signal to stop when we have eaten enough. We know these signals very well:

  Appetite: producing food-seeking behaviour and the desire for high-calorie foods

  Satiety: the feeling of fullness and lack of appeal of food.

  When I was in medical school, our understanding of these appetite and satiety drives – the on/off-switch of energy intake – was fairly basic. We were taught that low blood sugar levels stimulated the desire to start eating and that physical distension of the stomach sent messages to the brain to stop us eating.

  With the help of big-pharma-sponsored research, we now know that our appetite and satiety are driven by powerful hormones acting on the brain. Just like our thirst hormones, the satiety and appetite hormones act to change our behaviour without us using our free will to make a conscious decision. As we saw in the Minnesota Starvation Experiment (on pages 21–2), these hormones can literally drive you temporarily insane until the hunger is assuaged.

  Figure 4.1 The appetite and satiety hormones in the gut and fatty tissue

  Our appetite and satiety hormones are produced by the stomach, by the intestines and in the fat tissue (where the energy reserves are sensed). Both organs, the gastrointestinal tract (stomach and intestines) and the fat, are involved in well-regulated negative feedback loops: the hormones travel from the guts or the fat to the brain to ensure that we do not over- or under-eat. These feedback loops can be called the gut–brain pathway and the fat–brain pathway.

  The gut–brain signalling pathway controls our short-term, hour-to-hour and day-to-day appetite and satiety regulation. The fat–brain pathway controls our long-term (months and years) energy intake and expenditure.

  The Gut–Brain Signalling Pathway

  In the 1990s the hormones ghrelin and peptide-YY (PYY) were discovered in the gastrointestinal tract. Ghrelin is now known to be an appetite accelerator. It is produced in the upper part of the stomach and will increase its levels in response to food deprivation. It usually gets strong enough to tell us to eat at least three times per day. Once we have eaten, the level of ghrelin in our blood drops. Interestingly, it will also stimulate the reward centres of our brain, making food taste so much better when it finally does come along. The longer we go without food, the more we crave it and the tastier it is.

  Peptide-YY is produced by the cells of the small intestine in response to food that is inside the small bowel. Once food is sensed to have travelled from the stomach to the intestines, peptide-YY is released into the bloodstream and acts on the brain to produce a feeling of satiety. Not the uncomfortable feeling we get in our stomachs when we have overdone it at the all-you-can-eat-buffet, but the feeling in the brain we get once we have just eaten. There is no desire to seek food any more. The message is quicker and stronger if protein is sensed in the bowel.

  What happens to these hormonal appetite and satiety signals when food is restricted, either voluntarily through a calorie-counting diet or involuntarily when there is not enough food in our environment in a famine situation? In 2002, scientists at the University of Washington measured ghrelin levels in a group of obese volunteers before and after a low-calorie diet.1 The diet lasted six months and successfully resulted in a 17 per cent average weight loss among the group. Ghrelin levels were measured throughout the day and, as expected, peaked just before breakfast, lunch and dinner. After eating, the ghrelin levels subsided. This pattern – of high ghrelin before a meal and then low levels after eating – continued after the six-month diet had ended. However, the ghrelin signals were 24 per cent higher throughout the day compared to pre-dieting levels. As you can see from the graph, ghrelin levels after dieting were high all the time. In fact, after the diet, the mid-afternoon trough in ghrelin levels – the lowest they got after eating lunch – was similar to the pre-lunch peak that they experienced before the diet. The dieters were literally ravenous throughout the day – even after eating.

  Figure 4.2 The on-switch – appetite hormone levels before and after a diet Source: D. Cummings et al. (2002). Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Eng J Med, 346(21), May, 1623–30.

  This would fit in with how patients describe their appetite after a diet – constantly feeling hungry and having difficulty concentrating on anything but the next meal. When the next meal consists of the low-calorie foods that they have been told to eat, this can be a depressing prospect. The study confirms that appetite drives in dieters are at the very minimum at the pre-lunch levels of non-dieters – but very often much higher.

  The Off-Switch – Satiety

  What about our off-switch (the satiety hormone peptide-YY)? What happens to this after a diet? And are these signals changed over the long term even when we come off a diet? A separate study looked at a group of patients’ ghrelin and peptide-YY levels prior to dieting, immediately after a ten-week diet and then a whole year after the diet had finished.2 The results are depressing for anyone who has tried voluntarily to lose weight by calorie-restricting – but they do explain how dieters have been feeling. This study found that after the diet, ghrelin levels – and therefore appetite – were elevated, just as had been seen in the previous study. In addition, the satiety signal provided to the brain by the hormone peptide-YY was significantly lower. So the dieters were hungrier and when they ate they experienced more reduced feelings of satiety than they had before the diet. Sort of expected, but now we have the bad news.

  One year after the diets had finished, when the group had regained most of their weight, the levels of ghrelin (and therefore the appetite level) remained higher and the levels of peptide-YY (the satiety feeling) remained lower than pre-diet levels. Not only had the diets not worked to maintain weight loss, but the dieters’ appetite- and satiety-signalling remained disrupted a whole year after stopping their diet. Life had just got even more difficult for our group.

  Again, the results of this study match exactly what patients themselves describe after low-calorie dieting. Many express the feeling that their problems with weight regulation really started when their doctor or dietician (or, on many occasions, the school nurse) told them to try and consciously lose weight by low-calorie dieting. We will talk about diets in more detail in chapter 12.

  The conclusion? We already know diets don’t work
in the long term. What is emerging, though, is that diets can become counter-productive and can actually stimulate longer-term weight gain. The only way to lose weight is to understand what controls your metabolic and appetite drives – once you have this knowledge you can use it to adjust your weight to a healthier and more stable long-term level. Part Three of this book will guide you through these processes, but first it’s important to understand how your body-weight regulation works – only then will the changes set out in Part Three become a permanent part of your life.

  The Fat–Brain Signalling Pathway

  Our fat cells are in direct communication with our subconscious brain via a messenger hormone called leptin. This hormone is the powerful master regulator of our long-term energy stores – it works over weeks and months, rather than hours and days like the gut hormones. It controls both the long-term appetite and satiety drives (energy in) as well as the metabolic rate (energy out). Leptin is released by our fat cells and the amount of the hormone in the circulation mirrors the amount of fat that we have available as our energy reserve.

  The leptin messenger tells the weight-control centre of our brain the status of our current nutrition. This is the simple, but very powerful, fat–brain signalling pathway. It is a bit like the petrol gauge of our car, which shows us how full the tank is. Leptin levels are high when we are carrying a lot of fat and low when we are slim. If fat reserves are depleted, leptin will direct the brain to become hungry and to eat – to take in energy and preserve what we have. If fat reserves are plentiful, leptin will take hunger away and direct the body towards reproduction, or growth and repair.