Jamie Wiegertjes, now 30 years old, was already heavy as a baby. “My parents always paid a lot of attention to it, I was the only child at home with talent. But when I became more independent as an adolescent and was able to buy sweets myself, the kilos quickly came on.” Sonja Bakker, Weight Watchers, counting calories – even before he was an adult, Jamie’s weight regularly went up and down. “Lose weight quickly, stay very focused for a while, but as soon as things go wrong, you snap back.” He doesn’t even remember how many times he has lost and regained weight.
About eight years ago, Jamie lost 30 kilos in a short time with a crash diet. “I felt great, for a few months I really thought I was going to last. But even faster than I had lost weight, I was back to my old weight, even more. If I feel good about myself, it’s quite doable. But in the event of a setback, or if I have to go abroad for work, it still happens again.”
A good friend of Jamie has to make an effort not to lose weight, Jamie has the opposite: “It’s like I’m already gaining weight when I smell food. And after each time I lose and gain weight, it gets stronger, I have to do more and more to lose weight and it comes back faster.”
The yo-yoing is also playing tricks on him mentally, he says via the screen from his workplace. Jamie knows that biological changes in his body are working against him. “But it feels like a failure: I failed again. And when you have an ice cream, you feel the stares: would you really do that?”
Two and a half years ago, Jamie Wiegertjes stopped dieting and, he hopes, also stopped yo-yoing. “I am now committed to a healthier life. It takes longer, it comes in fits and starts, but since last year I have lost eight kilos and I have more muscle mass.”
Obesogenic memory
Why can one person eat apple pie every day with impunity, while another gains weight from just a handful of nuts? It is becoming increasingly clear why it is so difficult to stay slim once you have lost weight. And where the yo-yo effect comes from, that difficult-to-break spiral of losing and gaining weight.
Another hatch has recently been opened. Fat cells have an obesogenic memory, wrote Swiss researchers in October Nature. That would contribute to the yo-yo effect. The findings are a step forward in obesity research. But first a few steps back. Because the yo-yo effect has more than one track.
Roughly three biological mechanisms underlie yo-yoing, says Gijs Goossens, professor of cardiometabolic physiology of obesity at Maastricht University. Goossens conducts research into disturbances in the fatty tissue in people with severe obesity and the associated risks of cardiovascular disease and type 2 diabetes. He read the Naturestudy with above-average interest, because researchers in Maastricht are also looking at changes in different cell types in fat tissue.
A hunter-gatherer didn’t know when the next meal would come
Goossens starts with what is already known about yo-yoing. First of all, the metabolism adapts in people who lose a lot of weight. “The number of calories you burn decreases compared to your weight.” In people with a stable ‘healthy’ weight, the energy that comes in through food is in balance with the energy that the body uses. If you consume fewer calories than you burn for a longer period of time, your body will use the limited energy more efficiently and the combustion rate will decrease. “That makes quite a lot of sense from an evolutionary perspective. A hunter-gatherer didn’t know when the next meal would come. But it is striking: the decrease in energy consumption is stronger than you would predict based on the decrease in fat and muscle mass.”
After losing weight, you may weigh the same as a friend who has always been slim, but your resting energy expenditure is already lower. So even if you eat the same and exercise the same, you will gain more weight than that friend.
A second mechanism that promotes yo-yoing has to do with changes in the intestinal hormones that regulate hunger and satiety. The hormones that cause you to feel hungry increase after you have lost a lot of weight, while hormones that signal that you have eaten enough decrease. And the tricky thing is: the hormone balance remains disrupted for a long time, possibly for years, in people who have lost weight. That nagging feeling doesn’t go away.
The obesity medications that have been used to help people lose a lot of weight in recent years also affect that mechanism. These imitate the intestinal hormone GLP-1 and act on the receptor of that hormone. The appetite decreases and that helps people to eat less and lose weight. And to maintain the lower weight. But once they stop taking medications like semaglutide or tirzepatide, most people gain the weight back.
Then the third yo-yo track. This has to do with changes in the fatty tissue. One aspect is that after losing weight, less leptin is made in the fat tissue and enters the bloodstream to send a satiety signal in the brain. “The drop in that satiety hormone is also stronger than you would expect based on the amount of fat.”
In addition to fat cells, other cells, including inflammatory cells, also appear to play a role in yo-yoing. For example, inflammation in the abdominal fat can contribute to sugar being less well absorbed into the muscles.
Researchers in Maastricht also saw that the shrinking of fat cells during weight loss is mechanical puts stress on the ‘skeleton’ around the fat cells. “That stress makes cells want to fill up faster when calories come in.” That can also encourage yo-yoing.
By the way, Goossens says, it is not the case that people on a crash diet gain more weight than people who lose the same weight in more time. People who lose a lot of weight quickly do not necessarily gain more weight than people who lose weight slowly, he knows from research by his own department. In a group of 75 participants, half lost a lot of weight in five weeks with a diet of only 500 kilocalories per day. The other was given three months for this, with 1,250 kcal per day. Nine months into the diet there was no difference in weight gain between the fast and slow dropouts. “But we also know that it takes time to establish a healthy lifestyle. You cannot achieve that in a short time, like with a crash diet.”
Epigenetic memory
First, researchers looked at the fat tissue as a whole, gradually delving deeper into the cells. In Maastricht they also look at gene expression – the way in which genes are expressed – in individual cells. The DNA, the hereditary code, remains the same. But there may be changes in the functioning of the operating system that turns certain genes on or off. That’s where epigenetics comes into play.
The researchers who Nature wrote about the ‘epigenetic memory of obesity’, looked at humans and mice. First they examined the fat cells of people before and two years after a stomach reduction. They compared these with the cells of people who had never been obese and saw lasting changes in the genes.
They looked at how the genes were expressed in different cell types. They saw that genes involved in inflammation remained abnormally active. Genes for a healthy metabolism remained suppressed. In the people who had lost a lot of weight, the patterns appeared to be the same as when they were still obese. “You expect that changes that occur due to gaining weight will be reversed when you lose weight,” says Goossens. “But that does not happen completely.” And the researchers saw this in various cell types, including fat cells.
It is certainly not a matter of lack of willpower and discipline
But what exactly happened in the cells? To find out, the researchers put mice on a high-fat diet. They made the obese mice lose weight and then gave them lots of fat and calories again. Just like in the humans, they saw that inflammatory genes remained high in the slimmed down mice and genes related to combustion remained low. So combustion remained slow. Sugar and insulin levels were also higher in these mice after a meal, which is characteristic of type 2 diabetes.
They then went one step further in the Swiss mouse lab than in humans and looked at epigenetic changes, changes in the operating system in the cells. Using special techniques, they were able to discover how certain genes were unpacked and made active. They also saw that the way in which genes in fat cells are regulated was the same in the slimmed down mice as when they were still fat. This epigenetic change that persists after weight loss is what the researchers call obesogenic memory.
Arrive with just as much energy
But what does that mean? Goossens: “You see that the mice that were previously obese gain more weight than the animals that have always had the lower weight, even though they are fed exactly the same food.” That’s the crux. This was research in mice, but if this also applies to people, someone who was obese will gain more weight than someone who was always slim, even if the number of calories and exercise are the same.
The epigenetic changes are therefore on top of the other mechanisms that make it so difficult for people who have lost weight to stay slim. “Super important,” says Goossens. Also when you think about the stigma that people with obesity often face. “You often hear: you lost those kilos, right? Why don’t you keep it off? It is certainly not a matter of lack of willpower and discipline. This research underlines that, in addition to psychosocial factors, there are strong biological adaptations that explain why it is so difficult to maintain weight after losing weight.”
The question is: if changes occur in genes under the influence of environmental factors, diet in this case, can’t you reverse them? Can the obesogenic memory also wear out if you maintain a healthy lifestyle for a long time? “That sounds plausible,” says Goossens. “It won’t happen after two months, probably not even after a year. But who knows after about five years? We don’t know, but it’s a relevant question. “You sometimes hear success stories of people who stick with it for a long time. It would be interesting to look at epigenetic changes in them as well. And to look at the difference in gene expression regainers and maintainerspeople who yo-yo and people who maintain their weight after losing weight.”
There is more. For example, to what extent do parents pass on epigenetic changes to their children?
Goossens expects that studies into changes in different cells in fat tissue can make tailor-made treatments possible in the future. Suppose that inflammatory genes play a role in yo-yoing. “Then when losing weight, you can emphasize unsaturated fats with anti-inflammatory properties in your diet, such as olive oil and oily fish. And new drugs may be able to reverse the epigenetic changes, or biological adaptations in general.”
In an environment with ‘slim’ people, you always feel different. I now accept that I am the way I am
Jamie Wiegertjes recently registered at the Amsterdam UMC to have it examined whether he has a genetic predisposition to obesity – which he now knows is a chronic disease and not the result of a weak spine. If there are drugs that target those specific genes, he might use them. “Although I think losing weight is less important now. Above all, I want to stay healthy.”
As a board member of the Dutch Association for Overweight and Obesity he wants to help other overweight people who struggle with the same stigmas. “In an environment with ‘slim’ people, you always feel different. I now accept that I am the way I am. If I can show even one other person that he or she is not alone, my goal has been achieved.”