Why We Eat (Too Much) Page 12

  We also know that, in people suffering with severe weight loss through famine or illness, infertility rapidly ensues in order to protect the body against a dangerous and energy-sapping pregnancy. So leptin not only acts as the messenger to the metabolic and appetite areas of the brain, but also acts to switch on or off our reproductive ability, depending on our nutritional status.

  Leptin Resistance Can be Entirely Normal

  Leptin resistance causes weight gain by stimulating an inappropriate appetite when there are already ample energy reserves. It basically stimulates lots of energy in and gives us room to grow. There are two periods of our lives when leptin resistance can benefit us by helping to stimulate this growth:

  Pregnancy2

  Adolescence.3

  Healthy leptin resistance at these times is crucial to our survival – without growth and reproduction we would be extinct. But remember, in both healthy leptin resistance and obesity-related leptin resistance, the signs are the same – ravenous hunger (to take in energy) and fatigue (to preserve energy). We forgive our teenagers, and our mums-to-be, for this behaviour, but spare a thought for our hungry and tired sufferers of obesity – they are getting the same signals.

  What Causes Leptin Resistance?

  There are many theories in the scientific literature as to the cause of leptin resistance,4 and it is still being debated. But in my opinion the likely causes are a combination of:

  The hormone that controls the glucose level in our bloodstream – insulinfn1

  A protein that controls inflammation in the body called TNF-alpha, that triggers: inflammation of the weight-control centre of the brain

  the need for even more insulin.

  Insulin and Leptin

  We have learned that leptin is the long-term controller of our weight. When our fat stores increase, the level of leptin in our blood also rises. The hypothalamus, which controls our appetite and metabolism, uses the leptin level as a guide to how much fat we are carrying and will adjust appetite (how much energy we take in) and metabolism (how much energy we use up) according to the levels of leptin (and therefore the fat reserves). Leptin works by attaching to special cell receptors in the hypothalamus. The receptors act like a cellular letterbox where the message – too much fat – can be delivered. However, the strength of the leptin signal to the hypothalamus can be diluted by the hormone insulin.

  Both leptin and insulin send a signal to the same cells of the hypothalamus. The cells have separate receptors (cellular letterboxes) for either leptin or insulin. However, once the message is delivered, the signal pathways within the cell overlap each other. The cell cannot read both the insulin and leptin messages at the same time. So if insulin is acting on the cell receptor, then there is no room within the cell to read the leptin signal as well, even if leptin is present and posting its message. The leptin message therefore goes unread.5 As a result, the hypothalamus thinks fat stores are low (when they are excessive) and stimulates appetite while at the same time cutting metabolic energy expenditure. Just like the faulty fuel gauge in your car showing empty when the tank is actually full.

  High insulin ➞ leptin resistance

  The profound effect that insulin has on leptin resistance means it too becomes critical in the control of our weight set-point. Higher levels of insulin mean more leptin resistance and more leptin resistance means a higher weight set-point – and therefore a higher weight. We will discuss insulin in much more detail in chapter 10.

  TNF-Alpha

  TNF-alpha is released by cells that act as police against infection or injury. These cells (called macrophages) roam around our bodies looking for potential trouble (e.g. damaged cells or invading bacteria/viruses). Once trouble is spotted, the cellular police release TNF-alpha (think of police officers with pepper spray or a Taser) and this stimulates a cascade of events leading to inflammation (representing the arrest and disposal of the threat and repair of the damage). This is part of the normal inflammatory response.fn2 However, in obesity, once fat cells reach a critical size, the cellular police are called into action to investigate.fn3 They assume the swollen cell is damaged and therefore release TNF-alpha to start the repair process – but this can have untoward side effects.

  Obesity ➞ swollen fat cells ➞ increased TNF-alpha ➞ inflammation

  The chronic reaction of our bodies’ ‘police’ against swollen fat cells means that higher than normal levels of inflammation are always present. Obesity is a pro-inflammatory condition. This fits in with patients that I see in my clinic who suffer with obesity and are enquiring about bariatric surgery: all of these patients will have a positive blood test for inflammation (called a CRP test). Below I explain why this is critical to understanding obesity.

  TNF-alpha is also increased in response to a typical Western diet that has a low omega-3 to omega-6 ratio. We will discuss this in more detail in chapter 9.

  Western diet ➞ increased TNF-alpha ➞ inflammation

  Inflammation of the Weight-Control Centre

  We know obesity (and the Western diet) causes the production of TNF-alpha, which stimulates further inflammation throughout the body. All organs of the body are affected to some degree. There is a higher rate of inflammation in the blood vessels (causing heart disease), in the joints (causing pain and arthritis) and in the cells (increasing the risk of many cancers).

  But there is now emerging evidence that the inflammatory reaction causing obesity in the body also has a direct effect on the hypothalamus – yes, your weight-control centre, the area that depends on the leptin signal to calculate your weight set-point. And the result of hypothalamic inflammation is leptin resistance.6 The fat signal is not getting through – high levels of leptin are not being sensed – meaning that you perceive famine in times of excess.

  Obesity-driven inflammation ➞ hypothalamic inflammation ➞ leptin resistance

  From an evolutionary perspective, it makes sense that if we are sick or seriously injured the inflammatory response that is initiated also causes leptin resistance. Any injury will take energy to heal it, so an appropriate response would be to consume more energy than would normally be required (taking into account our current fat stores). This is achieved by blocking the effect of leptin, thus leading to increased hunger and subsequently more energy intake (in the form of food).

  TNF-Alpha Impairs Insulin Strength

  The other effect that TNF-alpha has on leptin is via its influence on insulin. When the level of TNF-alpha in the blood increases (as it does with obesity-related inflammation), it acts to block the effectiveness of insulin.fn4 7 Insulin becomes inefficient at doing its job of transporting glucose into cells (this is called insulin resistancefn5 in medical language). The result? More insulin is produced by the pancreas to compensate.

  Obesity-related inflammation ➞ increased TNF-alpha ➞ decreased insulin efficiency ➞ increased insulin ➞ leptin resistance

  An example of a healthy high TNF-alpha level is in pregnancy. TNF-alpha is produced by the placenta as the pregnancy progresses. It has a critical role in modulating the body’s immune response to the growing foetus.8 If immunity is not altered during pregnancy the foetus will be recognized as foreign and this will elicit an immune reaction against the baby that would end the pregnancy. As TNF-alpha levels increase in pregnancy, so does its effect on blunting the effectiveness of insulin. Diabetes in pregnancy (also called gestational diabetes) is common and increasingly researchers are recognizing the role of TNF-alpha as a causative factor in its development. As well as its beneficial effects on immunity in pregnancy, high TNF-alpha will lead to leptin resistance and stimulate the appropriate energy intake (and weight gain) of pregnancy.

  The effects of inflammation on leptin-signalling in the hypothalamus are beneficial in helping to balance energy reserves at times of injury, and helping the positive energy balance required for the growth of a pregnancy. But they become detrimental in obesity, driving further weight gain and increasing the risk of diabetes and heart disea
se.

  Now let’s return to the man at the Dubai breakfast buffet and see if we can explain his behaviour from what we have learned about leptin resistance. This man had very high leptin levels, in accordance with the amount of fat he was carrying. However, his large fat cells (1) caused a chronic inflammatory reaction and (2) led to high levels of TNF-alpha.

  The inflammatory reaction in his body attacks his set-point directly by producing leptin resistance in his brain.

  The TNF-alpha acts indirectly to produce leptin resistance by causing high insulin.

  The high insulin (stimulated by a Western diet and TNF-alpha) results in a blockage in the leptin-signalling in the brain.

  Finally, it is likely that this man has full-blown Type 2 diabetes, leading to even higher levels of insulin and even more pronounced leptin resistance. The result? An extremely obese man in a vicious cycle of voracious hunger and weight gain as a result of leptin resistance. It is almost as if his fat is acting like a tumour – encouraging itself to grow inexorably by sending the wrong metabolic signals to his body.

  Leptin Resistance Can be Reversed

  We know from animal studies that leptin resistance can be artificially reversed. Rats who are fed Western-type foods (high in sugar and oil) respond by developing insulin resistance – which leads to leptin resistance and then weight gain. When the animals are put back onto their normal diet, their leptin resistance and insulin levels stabilize and their weight returns to normal levels.9

  Higher insulin levels mean more leptin resistance. Unfortunately, our current Western diet predisposes us to high insulin levels. If we consume a meal or snack that contains a lot of sugar or processed carbohydrates like wheat, this will result in a spike in the amount of insulin produced (to process the glucose into our cells), and in the West we are surrounded by this type of food. (This will be discussed further in Part Two.)

  Figure 5.1 The vicious cycle leading to leptin resistance

  Summary

  We learned in chapter 4 that leptin, the hormone produced by our fat cells, is constantly working to try and keep our weight on an even keel. When we over-eat, and lay down too much fat, our leptin level increases. This is sensed by the weight-control area in our brain (the hypothalamus) and leads to powerful unconscious changes in our behaviour. Hormones work to decrease our appetite and increase our metabolic rate. Our food intake is lowered and energy expenditure increased – thus regulating weight gain. This is how most people, with only moderate effort, can maintain a regular weight for months and years.

  We learned in the present chapter what happens when leptin stops working. The message that we have enough fat – enough energy in reserve – does not get through. Like a faulty fuel gauge in your car, where, even though the tank is full, the gauge shows empty, you feel the urgent need to fill up.

  When there is a combination of high insulin and lots of inflammation in the body, leptin will stop working. The leptin ➞ insulin ➞ inflammation interaction becomes a downward spiral once it gets started. Insulin (caused by too much sugar initially) dilutes the effect of leptin. Inflammation (caused by a Western diet) stops the dilute leptin being sensed in the brain. Inflammation blocks insulin-signalling in the cells and so more insulin is needed. Even more insulin dilutes leptin even more … and so the cycle continues, leading to worsening leptin resistance. The brain perceives a lack of leptin (and therefore lack of fat reserve) and switches to survival mode. The result? As was demonstrated by the man at the Dubai breakfast buffet, someone who is already excessively obese is driven by the voracious appetite of a starving man to eat more and more. This is obesity, the disease, at its most extreme.

  But we also found light at the end of the tunnel. Studies show that leptin resistance can be reversed by changing the quality of the food that is consumed. This solution forms the basis of Part Three: how to lose excess weight and then maintain a healthier weight.

  Metabology

  We have now completed our short course in metabology: how the body deals with energy regulation, over-consumption of food and dieting. The crucial elements of metabology are the weight set-point theory and its effect on the vigorous defence of a fat store that is calculated by the subconscious brain to be appropriate and healthy (considering our genes, our current environment and our past history). Finally, we have seen what happens when a threshold of obesity is reached that leads to leptin resistance and the vicious cycle of obesity driving hunger and hunger driving obesity.

  SIX

  The Last Resort

  How Weight-Loss Surgery Works

  Do I shock you? We are very playful here. It’s a good tone for an operating theater. It is a theater, after all.

  David Cronenberg, Consumed (2014)

  The inspiration for this book, the reason I started to research the true causes of obesity, was the astounding effect that bariatric surgery has on people’s lives. I witnessed hundreds of patients, who had suffered with obesity for years, become transformed after the surgery. One of the most rewarding aspects of being a bariatric surgeon is the post-operative follow-up clinics, where we check on patients months and years after their surgery. It’s a great feeling when a patient says, ‘I owe my new life to you.’ I often come out of the clinic with shiny packages of wine or chocolate to be redistributed to my long-suffering administrative staff (who spend stressful hours on the phone with patients who have had appointments and operations cancelled because of the inefficiencies of the NHS).

  Quite often, if I have not seen a patient for six months after surgery, I will not recognize them when they walk into my clinic. The significant weight loss, combined with a change in their confidence and demeanour, mean that it’s only when they show me their old photo that I remember who they are (or were). When I see them for their annual follow-up, years after surgery, it’s usually just for a pleasant chat – they have changed their eating behaviour and enjoy cooking healthy, nutritious food.

  We have learned that it is impossible to sustain weight loss in the long term unless you have first reset your weight set-point to a lower level. The basic premise of this book is that we can only do this by adjusting the type of food we eat, changing our food culture, de-stressing, improving our sleeping habits and maintaining good muscle health. But what is it about bariatric surgery that makes it so successful in drastically lowering the set-point?

  We know that the hypothalamus, the part of the brain that controls our set-point, receives altered signals after bariatric surgery. The hormones that control our appetite and satiety drives are changed. These signals come from the gut. Bariatric surgery works by changing these signals by changing the configuration of the gut.

  Gastric Bands, Gastric Balloons and Jaw-Wiring

  In the early days of bariatric surgery, we thought that weight loss was achieved by one of two methods: either by a restriction of the amount of food that could be eaten, or by causing food to be malabsorbed. But we have now learned, through the usual medical mechanism – trial and error – that this is not the case. The gastric band (a plastic ring which is placed at the top of the stomach to stop you eating too fast), the intra-gastric balloon (a plastic balloon which is inflated in your stomach), or the old technique of jaw-wiring (where a dentist will literally clamp your teeth together) have all been shown to have poor long-term outcomes.

  The weight set-point of obese patients has not been changed by any of these techniques; they merely create an obstacle to the food being consumed. If you declare war on the set-point by having one of these procedures, then you will undoubtedly win the first battle. Yes, you will lose some weight. But then the set-point will take control to stop you losing too much weight, your metabolism will collapse and you will crave the high-calorie foods that will pass through the mechanical obstacle to your guts that your doctor recommended. It is sad to see tearful patients who have had these procedures blaming themselves for poor self-control. Commonly they will regain weight by consuming soft ultra-high-calorie foods like chocolate shakes or ice
cream. The formidable set-point defence has driven their appetite and food-seeking hormones through the roof – such signals (the same ones are produced after dietary weight loss) are too strong for us to ignore. The changed eating behaviour seen after weight loss in these patients, many of whom did not have a sweet tooth before their procedure, is driven by the change in these signals – not by any character flaw or weakness. This is the reason the gastric band, the intra-gastric balloon and jaw-wiring are increasingly being recognized as sub-standard – they do not alter the set-point and, as we now know, the set-point always wins the war.