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  In humans, increasing levels of blood sugar in pregnant mothers predicts a much greater risk of childhood obesity,24 and maternal obesity during pregnancy predicts a two- to threefold increase in obesity of offspring by the time they reach four years of age.25 Intriguingly, when obesity is ‘cured’ by bariatric surgery (i.e. gastric bypass), the children that the mothers had after their weight loss showed no sign of epigenetic transmission of obesity traits, compared to their older brothers and sisters who had been in the womb when the mother was still obese.26 Dr John Kral, from New York, who co-authored this study, explains that foetuses develop differently during pregnancy depending on their mother’s weight and general health – and such changes can be lifelong.

  Let’s just clarify what we are saying here, because it’s not looking good for future generations if they continue to be exposed to an environment that can trigger obesity. First, we found that genes have a 75 per cent influence on a person’s weight (remember the study of twins). Now we are saying that if your mother happened to be obese at the time of her pregnancy, she would pass on to you not only her half of your genetic DNA code (which may predispose you to obesity anyway), but also mutations that favour obesity (because your genes were incubated within an obese body).

  Why would over-nutrition, or obesity, during pregnancy lead to the development of traits that predispose the offspring to gain further weight? This seems to be counter-intuitive. We can understand why obesity traits are found in the genes of those babies who are predicted to grow in a harsh environment, but what is the advantage in terms of survival of having these traits if the food environment is predicted to be plentiful? The answer may come from the lack of micronutrients in the Western diet. Despite a mother being over-weight, she may have vitamin, mineral or other deficiencies because the processed food she is consuming doesn’t contain the same nutrition as old-fashioned fresh foods (we discuss this further in chapter 8). The genes in the foetus sense the deficiencies in the mother and the genetic expression of those genes is thus altered to ensure that enough foods are consumed in the future environment to avoid a similar deficiency. Scientists at Duke University have confirmed that administration of vitamin supplements to mice during pregnancy can profoundly alter the way the offspring look.27

  So there seems to be a U-shaped risk distribution for these traits. In cases where babies’ mothers were poorly nourished or had apparent over-nourishment, both groups of offspring pass on epigenetic traits encouraging the development of obesity in addition to any that are already embedded in their genes.

  Figure 2.5 Over-nutrition and under-nutrition of pregnant mothers can lead to a higher risk of offspring developing obesity in adulthood. Studies have described a U-shaped relationship between birth weight of babies and the propensity to develop obesity in adulthood Source: S. Parlee and O. MacDougald (2014). Maternal nutrition and risk of obesity in offspring: the Trojan horse of developmental plasticity. Biochim Biophys Acta, 1842(3), March, 495–506.

  The School Visit

  I remember a visit to an all-girls secondary school with my daughter a few years ago. We were in the process of selecting her next school. What struck me more than the familiar drabness of a London comprehensive was the size of the pupils. The girls who politely showed us around and waited to answer our questions were really suffering – or at least a large proportion of them were – with significant weight or even full-blown obesity.

  At the time, I asked myself: how can the proportion of obese children be so strikingly different from my own schooldays? The food that we consumed was quite unhealthy then; how could it be so much worse now? What I had not considered at the time, and what has become clearer since, is the contribution that epigenetics makes to obesity risk. It was not just the environment (which had not changed much) or the children’s genes (which would not change much from the previous generation) that drove their weight – epigenetics was a major factor. The obesity in these children was contributed to by epi-mutations that amplified the difficulty they had in maintaining a healthy weight. The mothers of these children, who would have been born from the late 1960s into the 1970s, would have been exposed to the first wave of the obesity epidemic that affected the population in the early 1980s. Many of the mothers would have been obese during their pregnancy and involuntarily promoted epi-mutations that increased the risk of obesity in their children.

  Generational Shift in Obesity Risk

  If epigenetics really does contribute to obesity in offspring, this may explain the worrying generational shift in obesity risk, with young people being increasingly primed with stronger and stronger obesity traits. Every generation harbours dangerous epi-mutations from obese mothers or grandmothers. Even if our diets stayed the same over the next few generations, obesity will become much more commonplace due to the increasing occurrence of these genetic traits. Remember this when you next see adolescents struggling with obesity. Not only are they having to cope with the normal teenage angst of growing up, but also with much stronger obesity traits than any previous generation.

  It sounds depressing, but there is a silver lining. If we understand the risk, we can pre-empt it through education. If future mothers are aware that the risk of obesity transmission to their offspring is reversible, they will be much more likely to try and attain a normal weight before pregnancy (hopefully with the help of this book).

  The other strategy – for drug companies and scientists – would be to target the obesity genes with their own tailor-made epi-mutations in order to reverse the effect of the gene. In fact, the first ground-breaking study into epigenetics did exactly this. Scientists at Duke University in America were looking at the effect of vitamin supplements on mice, and their offspring, during pregnancy.28 But the mice they were using were not ordinary mice. The agouti mice had been specially bred to have two traits: obesity and a yellow coat. If a male and female agouti bred, their offspring would always turn out to be just like their parents – large and yellow. When scientists added a simple vitamin supplement into their food, they found that the pregnant agouti mice produced offspring that were brown and … skinny. They analysed the genetic code of the offspring and found that the reason the mice had lost their obesity and yellow colouring was that the vitamin supplements had stimulated epi-mutations that had switched off the genes encoding for obesity and coat colour. This research offers us a glimpse into the possibilities of using epigenetics as a treatment for obesity in the future.

  There are many different genes that can contribute to people being either obese or lean. One of the first to be identified was the FTO gene. We know people with this gene are on average 3kg (half a stone) heavier than those without the gene. And there are several other genes so far identified that alter the chance someone will be lean or obese. Some of these genes encode for appetite and some for fullness. They determine the amount of food someone will naturally want to eat. They also encode for metabolism, i.e. the amount of energy someone will burn off. We will see later in this book the extent to which metabolism is fundamental to weight control.

  If we can eventually target and switch off, using epi-mutations, genes that have been identified as promoting strong appetite or low satiety or low metabolism, we will go some way to fixing the problem of obesity. For now, this is still a long way off.

  Keep It in the Family

  As far as a genetic predisposition to obesity is concerned, my patients have been telling me about this for years: ‘It’s in my genes, doc’; ‘I’m from a family who suffer with their weight.’ Time and time again they will walk in with close blood relatives who are also clearly suffering with their weight. Quite often, once one member of the family has undergone successful weight-loss surgery, other members will follow their lead.

  I once did a rare domiciliary visit to a patient’s home to assess her for surgery. Her size affected her so much that she couldn’t easily make it to the hospital. She weighed 200kg (over 31 stone). I remember the visit because I do not usually see patients in their
own homes. The house was tidy and welcoming, and she had photos of family members scattered around on the mantelpiece, tables and walls. All of them suffered with severe obesity, but were clearly trying to get on with their lives. It really struck me the powerful effect genes can have in predetermining whether you are going to struggle with weight control or not.

  CASE STUDY – LIKE ATTRACTS LIKE

  A sixteen-year-old Jewish boy came to my clinic with his parents to discuss how best to treat his weight. They were keen for him to get married in the next couple of years, as is the norm in the orthodox Jewish community, but they were concerned his weight might put off future wives. They said they had put him on lots of different diets, but nothing seemed to work. What struck me was the size of the parents. The boy was large, but both his parents were also overweight. The interesting part of this story is that when the parents got married there was no opportunity for bariatric surgery to reset their weight, so their focus was now on helping the younger generation to overcome the obstacles they had been unable to deal with. I could imagine that they, and their families, ended up settling for someone of a similar size in the absence of other suitors. This is an example of what is called assortative mating, where couples attract mates with similar characteristics. In this case that characteristic was their obesity. The unfortunate boy had the triple whammy of receiving obese genes from both parents and also obesity-causing epi-mutations as a result of his mother being obese during her pregnancy. In addition to this he lived in an environment with a Western-style diet, and so his obesity genes were triggered. He was a typical example of someone who was almost preordained to become obese.

  Summary

  So, how does a sacred cow in India explain the cause of the human obesity crisis in the world? Let’s recap what we have learned so far.

  Farmers can make cows grow bigger by:

  Feeding them an unnatural special diet (grain/oil mixture)

  Selectively breeding the bigger cows rather than the smaller cows (unnatural selection).

  We found that when it comes to humans we are just like the cows in neighbouring farms. Human populations become more obese:

  When they are fed a Western diet (grain/oil mixture)

  When a population has experienced extreme trauma (famines, migrations) that selected only the largest and most metabolically efficient to survive (natural selection, or ‘survival of the fattest’).

  A human population that has survived extreme trauma will become enormously obese if exposed to a Western diet (Pacific Islanders, Pima Americans).

  In addition to our genetics and environmental obesity triggers we looked at the new area of epigenetics. This confers an added layer of risk directly onto the genes of people whose mothers experienced famine, or obesity, when they were pregnant. This explains why each generation of our children suffers even more with obesity.

  The latest research on this topic seems to validate the explanation ‘It’s in the genes, doctor’, which my patients have been telling me for years. This reassures me that we are now on the right track.

  Our stressful, sedentary and sugar-laden lifestyles don’t affect everyone in the same way, however. Some people can breeze through life without a thought for their waistline and remain slim; they seem somehow to be protected against obesity, almost as if they are immune to it. Other people go through their lives being stalked at every corner by the spectre of obesity, trying desperately to run away from it (sometimes literally, in the gym), and constantly dieting.

  Our genes and our epigenes, triggered by our environment, control our own personal weight set-point. Just like farm animals, most humans have little personal choice as to what size they end up – skinny, slim, average, big or obese. If you happen to have the wrong genes in the wrong environment, then it is almost preordained that you are going to struggle with weight control – it’s not your fault. If you try and fight against your weight set-point and consciously attempt to manipulate your weight downwards by dieting, you may, as the next chapter explains, make things even worse. The solution is to create your own personal environment, one that insulates you from those obesity triggers that your genes are looking for.

  The final section of this book offers a practical, long-term plan for what to do. But to start things off, if you are struggling with obesity, in my experience the best solution (other than bariatric surgery) is to understand why your brain wants a high weight set-point. What signals is it receiving that makes it think it needs extra fat stores? These signals are the key to obesity and how to control it.

  THREE

  Dieting and the Biggest Losers

  Why Our Metabolism Can Change Dramatically

  I sometimes watch the reality TV show The Biggest Loser with dismay. You are probably familiar with the show’s content. The producers select people who are seriously obese and put them through an intensive, thirty-week programme of dieting and physical exercise. The show follows the contestants as they shed the pounds. It sympathizes with the great effort that they are making, focusing on their grimacing faces as they sweat the weight off in the gym. The personal trainer yells threats in their face like a boot-camp sergeant major if they waver in their efforts. But, as the show goes on, we see that all the work that the contestants have put in appears to be worth it.

  It’s ironic that most of the ads during the breaks in this show are for delicious-looking fast foods and as the programme progresses you get more and more hungry. The show usually ends (while you are devouring a pizza delivery) with smiling contestants being amazed to see exactly how much weight they have actually lost when they stand on the scales. The weight loss can be up to 80kg (over 12 stone), that is, the same weight as an average man! The results seem to be incredible – it’s entertaining to watch and pulls in large audiences. But what is the real aim of the show, and all similar boot-camp-type weight-loss shows? Their conclusion is that people really can lose huge amounts of weight if they put the effort and application into it. A secondary message is that if you can’t do this, you must be weak-willed, greedy or both. These sorts of TV programmes are a major boon for gyms and diet books, but do they really help people who are trying to lose weight?

  What The Biggest Loser fails to show is the long-term effects on the contestants. We are supposed to believe that the new life the show has given them will be permanent. They are saved, with all the effort they have put in, and have finally beaten obesity.

  How does the outcome of The Biggest Loser fit in with our weight set-point theory? We can assume that unless the contestants have been able to permanently alter their weight set-point downwards, then the subconscious brain would work to bring the weight back up again, using the negative feedback systems controlling appetite and metabolism.fn1

  The Biggest Losers in the Lab

  Let’s look at a famous study from one of the National Institutes of Health, in Bethesda, Maryland, in the US, conducted by Dr Kevin Hall, a physicist intrigued by the seemingly irregular rules of human metabolism. His team followed up fourteen contestants in The Biggest Loser shows and analysed what had happened to their weight and metabolism six years later.1 The participants had initially lost on average 58kg (9 stone 2lb) each, an amazing result considering how obese they were when they were selected to participate. However, six years after the show, they had regained an average of 41kg.

  Was their weight set-point still working against them as far as their metabolism was concerned? At the end of the competition their metabolic rate was recorded as being 610kcal lower than when it started. Six years afterwards their metabolisms were even more depressed, at over 700kcal less than they were before the show.fn2 This constituted a serious decline in their metabolic rates and meant that just to maintain their weight they had to either consume the equivalent of a large three-course meal less, or alternatively go on a 10km run every day compared to their pre-diet metabolism. It seems that the contestants’ weight set-point was indeed the same as before they were dieting and that their negative feedback sys
tems were doing all they could to win the war and regain the weight that the subconscious brain wanted – despite conscious efforts by the contestants against this.

  I Can Lose Weight, But …

  This would confirm what patients tell us repeatedly about dieting. Yes, it is possible to lose weight in the short term, but in the long term they always regain it. It is because the subconscious brain always wins the battle of wills against the conscious brain.

  Figure 3.1 Changes in metabolism six years after The Biggest Loser show Note: Contestants who had kept more weight off had much lower metabolisms compared to contestants who had regained weight, demonstrating the weight set-point working to change metabolism years later (statistically significant r = 0.59; p = 0.025)

  Source: E. Fothergill et al. (2016). Persistent metabolic adaptation for 6 years after ‘The Biggest Loser’ competition. Obesity (Silver Spring), 24(8), August, 1612–19.

  Is dieting detrimental to our long-term metabolic health? If we have been on regular low-calorie diets for many years, how will this affect our metabolism? Will it be lower than when we started dieting? We know from the dietary studies already mentioned that metabolism decreases with weight loss. There is growing evidence that repeated weight loss and then weight regain – so-called weight-cycling or yo-yo-dieting are detrimental to future weight loss. A study from Korea has shown that people who have frequently dieted lose less fat, and more muscle, when dieting compared with non-weight-cyclers.2