Obesity – a struggle against ourselves

The obesity epidemic began in the USA somtime in the 1950s and 1960s, but it became clearly noticeable in the America society in the 1980s. In Sweden, the epidemic began to show clearly during the 1990s and is now fully evident. Currently, half of all adult Swedish males, just over one third of all women and every fifth child is overweight or obese.

Text: Fredrik Hedlund, first published in the magazine Medical Science 2015.

There are many theories and explanations about what caused this dramatic development. However, it essentially boils down to that obesity is due to eating more than you need to. And there are researchers who argue that this is exactly what we have been deceived into doing.

“What mainly happened over this period was the fast food invasion. I think this is the primary explanation for the current obesity epidemic. What characterises fast food is that it has an extremely low nutritional content, but an extremely high calorie content. It’s full of fat, sugar and salt and these are what light up our taste-buds and brain,” says Erik Hemmingsson*, researcher at the Department of Medicine at Karolinska Institutet and tied to the Obesity Centre at Karolinska University Hospital in Huddinge.

We return to Erik Hemmingsson and his discussion, but first a few important things about fat need to be explained.

Fat is good. We would not survive without fat. Fat is the body’s most important energy store. Fat is used as fuel in all of the body’s cells and is also found in the surface structure and membranes of cells.

Some people have adipose tissue that does not form properly. This is a very rare condition that demonstrates what happens when fat storage does not work as it should.

Ingrid Dahlman. Photo: Stefan Zimmerman

“These patients have very high levels of lipids in their blood and diabetes that is hard to treat. The body needs a warehouse where it can store energy for short periods. If it doesn’t have this, storage takes place in the liver and muscles and this means a huge impact on metabolism,” says Ingrid Dahlman, researcher at the Department of Medicine, Karolinska Institutet. Interestingly enough, these are the same complications seen in obesity.

“This shows how important the adipose tissue is for storing reserves. We think that there is a similar mechanism in common obesity. When someone eats too much, the excess is stored in the fatty tissue. But when the ability to store energy in the fatty tissue is exceeded, this spills over into the liver and muscles and causes disorder there,” says Ingrid Dahlman.

Fatty tissue not only a storage space

For a long time, the fatty tissue has only been regarded as a static storage space for fat. However, researchers have recently begun to understand that the fat cells and the fatty tissue they form is much more complicated. About 20 years ago, it was demonstrated for the first time that the fatty tissue also functions as a gland that produces hormones, enzymes and inflammatory proteins.

Professor Peter Arner. Photo: Stefan Zimmerman

“Fat is the body’s biggest producer of proteins. This is actually pretty surprising. It is believed that thousands of proteins are produced in the fat, but we have not yet come close to charting them all,” says Peter Arner, professor at the Department of Medicine, Karolinska Institutet, who has been studying fat for 45 years.

One of the hormones from the fatty tissue that has been identified is leptin. It is perhaps most known because of the leptin mouse, which very clearly demonstrates the effects of this hormone. The leptin mouse lacks the ability to produce leptin as a result of a mutation and has an enormous appetite, which means it quickly becomes so fat that it can easily weigh more than twice what a normal mouse does.

Leptin signals satiety. Another fatty tissue hormone, ghrelin, signals hunger and together these two work as the backbone of hunger/satiety regulation. Other hormones from the fatty tissue contribute to regulating sugar turnover and blood pressure, for example. But the fatty tissue is complex in more ways than this. For example, there are two different types of fatty tissue, which have different densities. People either have lots of small fat cells or a small number of large ones. But there is no connection to whether the person is fat or thin. However, there are great medical differences between the different types of fatty tissue.

“Having a small number of large fat cells is bad, as these people are at an increased risk of diabetes, insulin resistance, elevated blood fats and elevated blood pressure. So it’s bad to have few large fat cells and good to have lots of small ones,” says Peter Arner.

Why people have different type of fatty tissue is still not entirely clear, but Peter Arner and his research group have recently published an article describing the first gene regulating this.

“A transcription factor called EBF1 (Early B Cell Factor 1 ), appears to regulate the number and size of fat cells,” he says.

In this article, the researchers also show that EBF1 is down-regulated by inflammatory signalling substances in the fatty tissue, which could explain why some people have fewer fat cells than others. But the exact link has not yet been demonstrated.

Regardless of cause, the fact remains that it is good to have many small fat cells and bad to have few large ones. The reason being that large fat cells behave differently than small ones. Even if the researchers do not know exactly how it happens, the effect is that the large fat cells release more waste products such as fatty acids, which is bad for the body. But there´s more to it.

“The fat is also more inflamed in those who have large fat cells than in those with small fat cells, which in turn can affect hormones controlling blood pressure and insulin sensitivity,” says Peter Arner.

According to Peter Arner, having good fat is more important than the quantity of fat you have. This may explain why some fat people are still healthy and completely free of the metabolic effects of obesity. The size of the fat cells also says more about metabolic health than the Body Mass Index (BMI) does.

Consequently, it would actually be good if there was some form of test for fat cell size. And this is possible, but it is not a routine test that can be carried out at a primary care centre today, perhaps it will be in the future, thinks Peter Arner. But until then, he has a simple test that anyone can do themselves.

“We have released a measure that we call one metre waist. If your waist circumference is more than one metre, you are in the danger zone. You measure with a measuring tape at the navel, it is really simple. Those who have a large waist often have large fat cells,” he says.

Size matters

In the same way that fatty tissue was believed to be nothing but a storage space for fat, until five or six years ago it was also believed that people’s fat cells stayed the same throughout their entire lives. This was also wrong.

Kirsty Spalding. Photo: Ulf Sirborn
Kirsty Spalding, photo: Ulf Sirborn.

Some years earlier, Australian researcher Kirsty Spalding had moved from Australia to work at the Department of Cell and Molecular Biology at Karolinska Institutet. Thanks to a revolutionary new method using carbon-14 to determine the age of cells, she was able, together with Swedish researcher Jonas Frisén, to demonstrate that our brain cells are renewed.

The carbon-14 method is normally used to date archaeological finds or establish whether Renaissance paintings are genuine by measuring the remaining radioactivity in carbon-14 that has a half-life of just under 6,000 years. This is dealing with thousands to hundreds of years. Kirsty Spalding now used the same technique to determine the age of cells down to individual years.

“We are able to do this because of the atmospheric nuclear weapon tests carried out in the middle of the 1950s and the beginning of the 1960s. Atmospheric bomb-testing created a massive increase in carbon-14 in the atmosphere between 1955 and 1963, called the bomb spike. In 1963 a test-ban treaty was signed, limiting all above-ground nuclear bomb testing, resulting in an exponential decrease in atmospheric 14C levels. We are not completely down to the levels prior to the bomb-testing period, but we are getting close,” she says.

By studying cells from people born at various times along the time axis from about 1920 until present, it is possible to show whether cells have been renewed during a person’s lifetime.

By accident, Peter Arner came into contact with Kirsty Spalding who, after a bit of adjustment, was also able to use her method on fat cells. They appeared to be replaced many times over a person’s life.

“We gain about 10 per cent new fat cells each year. In 8.3 years we have exchanged approximately half of our fat cells,” says Kirsty Spalding. But this turnover of fat cells is strictly regulated, with the birth and death rate of fat cells balanced in weight-stable individuals. Cross-sectional studies indicate that fat cell number is stable in adults, even following significant weight loss. However, crucial longitudinal studies, where individuals and their number of fat cells are followed across the lifespan, are missing from the literature.

“The number of fat cells appear to be very stable over short periods, and even people who dramatically lose weight retain the same number of fat cells. But I have a hard time believing that people who become extremely fat only increase the volume of their fat cells. In addition, there is at least one study showing that women who gain weight can increase the number of fat cells they have in their thighs, so I think that under certain conditions we can gain more fat cells, as least in certain tissues,” she says.

The environment more important than heritage

But just because it is possible to increase the number of fat cells, it is not necessarily as easy to go in the other direction, something which may explain why it is so hard to lose weight.

“We may be programmed in a way that allows us to increase the number of fat cells when gaining weight, but there is little evidence that we can reduce the number of fat cells we have. There appears to be some function that retains the higher number of fat cells despite going on a diet and losing weight,” says Kirsty Spalding. In which case, this is bad news for all those who want to lose weight.

“Yes, it is definitely a signal to take care of yourself at an early age. Because the number of fat cells appears to be maintained and if you have an increased number of fat cells when you are young, everything points to it being impossible to reduce this number later in life.”

But what is behind the obesity epidemic that has suddenly affected humanity? As with many other diseases, it is a combination of heredity and environment, but researchers are in agreement that genetics are not the decisive factor. 

Professor Claude Marcus. Photo: C Meadow

“It is usually said that 60–70 per cent is genetics and the rest is environmental factors. But if you think a little further, you might realise that this is not the case actually; because you’ll never become fat if you don’t eat too much. From that perspective, you could say that it is always environmental factors. If you don’t eat too much, you don’t develop obesity, regardless of your genetics,” says Claude Marcus, professor at Karolinska Institutet and research supervisor at the Swedish National Childhood Obesity Centre at Karolinska University Hospital in Huddinge. Not even Peter Arner, who has recently published a paper on his discovery of the first gene controlling fat cell development, argues that genetics is of vital significance.

“There are many who want to believe that you become fat because you have a problem with your metabolism, and this might be the case for a few people, but I have to say that the most common cause is eating too much and not getting enough exercise. Those who put on weight more easily are those who eat a little more and move a little less than others. There are quite a large number of studies indicating that this is the case,” he says.

But what is it that makes people eat more than they need to? Most evidence points to a combination of social and psychological/emotional factors. In the West, there is a very distinct link between obesity and low socio-economic status. Those who become obese are often poorly educated and poor.

Erik Hemmingsson. Photo: Ulf Sirborn

“I believe that the social environment in which people grow up affects them a great deal. If the parents are poor, then we know that the incidence of substance abuse is higher, there is less of a social safety net, there is more exclusion, there is more criminality, quite simply more misery,” says Erik Hemmingsson*.

He has recently published a completely new model of how psychosocial and emotional stress contributes to obesity.

“My theory is that there is a very detrimental impact on children who grow up in an insecure environment, in contrast to children who grow up in a secure and harmonious environment. This impact includes effects on stress, metabolism and compensatory habitual patterns,” he says.

Claude Marcus, who has studied childhood obesity, for example in “Early STOPP” (Stockholm Obesity Prevention Project), can confirm the clear link to low socio-economic status, and that the effects on weight begin very early.

“As early as at one year old, we see that children of poorly educated parents are a little bit more obese than those of well-educated parents. We are not quite sure why.”

But a comparison with the results of a similar study Claude Marcus’ research group is conducting in China clearly indicates that this effect is dependent on social factors. There it is instead the children of well-educated parents who are obese.

“There, it is still considered a status symbol to give their children soft drinks and go to McDonalds,” he says. Claude Marcus’ most plausible explanation is close to Erik Hemmingsson’s theory about insecurity, but among the parents.

“We believe that some form of insecurity results in the children being given too much food because their parents believe they might be getting too little,” he says. Otherwise, things are generally going in the right direction in Sweden at the moment, but not in all groups.

“For children, primarily younger children, things are looking better now than they did five or six years ago. Nevertheless, it appears that segregation is on the increase. What I mean to say is that obesity is increasing among children in lower socio-economic groups, while in others it has plateaued or is decreasing,” says Claude Marcus.

Consequently, we should be targeting more interventions at lower socio-economic groups, he argues.

“There should be a huge opportunity to have an impact on the situation via paediatric primary care centres, with the help of specific support to families in more socially disadvantaged areas,” says Claude Marcus.

Interventions in schools

Another way to combat excess weight and obesity is to work much more purposefully in schools and preschools. Several years ago, Claude Marcus conducted an experiment in which a number of schools with associated after-school recreation centres began having more physical activity during lesson time, improve the quality of school lunches and have zero tolerance to sweets in school at the after-school recreation centre. These would then be compared with schools and after-school recreation centres that had not changed, control schools.

“We randomly selected which schools would change and which would stay as they were. But not all schools wanted to be involved; none of them wanted to be in the control group and we begged and pleaded to those who were in that group not to do too much, but they still did a bit. But what they didn’t do was to introduce zero tolerance to sweets as this was the hardest to implement,” says Claude Marcus.

After four years, the researchers could still demonstrate a statistically significant difference between the schools, with pupils in the schools who changed having a lower prevalence of obesity. It appeared that the children had also begun eating better at home.

“They ate fewer sweets, less fatty milk products and more fibre-rich bread than pupils in the control schools. Our hypothesis is that many parents want to say no to sweets as an everyday thing, but that it is difficult if professional educators think it is OK. We mainly saw differences among poorly educated parents. So one of the answers to the question of how to reach those who need it most are for schools and after-school recreation centres to do this indirectly by setting a good example,” he says.

But for the children who are already obese, they cannot simply wait and see if it is a passing phase, rather they have to seek help as soon as possible. The older the child is, the harder their obesity is to treat.

“At the age of six or seven, there is a treatment effect over three years that has a definitive impact on health in 90–95 per cent of cases. After this, there is an almost linear decrease. If treatment begins when the children are 14–15 years old we see pretty much no effect, we succeed in less than five per cent of teenagers. The message is that you have to begin treatment early, before ten years of age,” says Claude Marcus.

The researchers argue that the society we have created is one of the primary causes of the obesity epidemic. A society where everything is available, pretty much whenever you want, and an attitude to food that has changed dramatically.

“Twenty-five years ago, it was unseemly to walk along the street eating something. You would sit down to eat and would not snack between meals. Now it is standard behaviour to walk and eat and snacking is not considered immoral anymore,” says Claude Marcus.

Erik Hemmingsson also indicates that the changes in society of the past 30–40 years are the main cause of obesity. He points specifically to the explosion of fast-food restaurants such as McDonalds, Burger King and the like.

“Without a doubt, the fastfood industry bears a huge responsibility,” he says. It is even more unfortunate that these chains attract children with toys and figurines from the latest Disney films, he argues. Children do not want to go there for the food; they want to get the toys, but they learn to associate them with fast food. And the parents are happy that their children want to eat.

He also argues that contemporary production methods create products that are not as good as they were in the past.

“The food we ate 100 years ago, that had grown slowly in the earth, was full of nutrition. The food industry now forces production in order to get more in a shorter time, which dilutes the nutritional content,” he says. He therefore argues that we should choose organic vegetables and meat and prepare food from scratch instead of eating fast food and highly processed partially prepared products in order to make food as nutritious as possible. Claude Marcus argues that we have gone too far and must return to certain old principles that were actually pretty sensible. One of these is regular mealtimes. Today, when everyone in the family has different activities in the evening, the way mealtimes are organized has been completely changed in many families; this contributes to the development of obesity, he argues.

“I believe that one of the most important factors is the regularity of food intake and not snacking between meals. I argue, almost a little neo-moralistically, that everyone should eat breakfast, lunch and dinner at the same time and only eat fruit in between times. And drink water or skimmed milk with your food,” he says.

Calorie-rich drinks such as soft drinks and juices should not be consumed with everyday meals, he argues. Not only do they contain empty calories, but we also have a really hard time evaluating liquid calories. When it comes to solid food, we have a sort of calorie memory, which means that we do not feel as hungry the day after having eaten a big dinner. The body controls its intake of calories in this way and maintains it at a relatively constant level over time. But this does not work at all as well with liquid calories.

“There could of course be an evolutionary explanation for this. Calories in liquid form have not existed for more than a few hundred years,” says Claude Marcus.

If contemporary society strongly contributes to people becoming overweight and obese, the human body makes the greatest possible contribution to maintaining the increase in weight. Those who try to lose weight are really embarking on a battle against nature.

“When you lose weight, the size of the fat cells decreases. But this also lowers their metabolism, which means that the energy requirement goes down. In addition, they release a smaller amount of the satiety hormone leptin, which makes you more hungry. The entire system appears to be rigged in order to maintain the body weight you have attained. The whole of nature is working against weight loss,” says Kirsty Spalding.

Something that all those who have tried to lose weight can testify to. This is also seen clearly when different treatments are evaluated scientifically. There are plenty of reviews of different diets, pharmaceutical treatments, exercise and other activities that are used for weight reduction and they all show the same thing. Treatment can lead to an average weight loss of up to eight to ten kg over the course of six months to a year that can be sustained for a few years thereafter. But sooner or later, most patients return to close to their initial weight or, not uncommonly, exceed it. What is difficult is not losing weight quickly, but maintaining the new weight and avoiding a weight rebound.

Surgery has lasting effect

Erik Hemmingsson recently published an analysis of 20 different high-quality studies encompassing over 3,000 people, which investigated different methods for avoiding this weight rebound. Following an extremely low-calorie diet that resulted in an average weight loss of just over twelve kg, the participants were randomly assigned to different weight maintenance treatments or to the control group. The comparisons falter a bit as the treatment times varied from three to 36 months in the different studies, but it shows that meal replacement was successful in reducing the weight rebound by 3.9 kg, medication by 3.5 kg and a high-protein diet by 1.5 kg, while exercise and dietary supplements did not successfully affect the weight rebound at all.

“Despite some strategies being able to reduce the weight rebound, the effects were without exception modest, which clearly reflects the limitations of lowcalorie diets,” says Erik Hemmingsson.

The only method that has so far been shown to result in significant and enduring weight loss is bariatric surgery. The SOS (Swedish Obese Subjects) study, run from the Sahlgrenska Academy in Gothenburg, monitors patients who have undergone obesity surgery and compares them with a control group whose obesity has been treated in other ways. The study has recently published 20-year data.

Martin Neovius. Photo: Kate Gabor

“On average, those who had surgery are about 20 kg lighter after 20 years, while the controls are near their baseline weight,” says Martin Neovius, researcher at the Department of Medicine, Solna, at Karolinska Institutet.

The most frequently used method of surgery in Sweden today is the gastric bypass, which involves food being directed past the stomach directly into the small intestine. It is an extreme method, but it works and the weight loss also has an impact on other obesity-related morbidity.

“Aside from the weight loss, we have seen a reduced risk of myocardial infarction, stroke, cancer among women, early death and diabetes, as well as an increased chance of maintaining diabetes remission among diabetics,” says Martin Neovius.

However, in spite of these good results, simply using surgery to defeat the obesity epidemic is not an option. Rebuilding the entire gastro-intestinal anatomy to force changes in behaviour, which has both lifelong consequences and, as with all surgical interventions, involves some risk is a far too extreme method that should only be seen as the last option for a limited number of patients.

Consequently, there are somewhat strict criteria stipulating who can be considered suitable and this is primarily based on BMI, something which is now starting to be increasingly called into question, explains Martin Neovius.

“There is a whole lot of data pointing to BMI in itself not being a particularly good selection criterion. Instead, it appears to be a better idea to select patients based on diabetic status.”

Discussions are ongoing regarding how to change the selection criteria. But in Sweden, people with a BMI lower than 35 who have a worse diabetes profile are already sometimes undergoing surgery.

But if it is not possible to perform surgery on all obese people and other treatments only have a marginal effect, something different must be done to deal with the obesity epidemic. And researchers believe that this is coming.

Peter Arner argues that there are many possible approaches that could be employed by future treatments.

“You could tackle the turnover of fat cells and their fat content, halt the breakdown of fat a little or perhaps affect the hormones and inflammation in the fatty tissue,” he says.

Kirsty Spalding also sees several possible paths to a future enduring weight loss, even though she cautions that this must be done in a controlled way and with care.

“One way could be to negatively adjust the number of fat cells at the same time as weight is lost via dietary changes in order to make it easier to maintain the new weight. Another interesting way could be to activate adipose tissue to burn fat rather than store it. This is a newly evolving field built on the recent exciting findings demonstrating brown and brown-like depots of fat in adult humans. Brown and brown-like fat burn energy, rather than storing it.

*) Erik Hemmingsson is no longer working at Karolinska Institutet.

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