Surely you’ve heard someone complain about having regained the kilos they had worked so hard to lose with a low-calorie diet to lose weight, or it may have even happened to you. This is known as the ‘rebound effect’ or ‘yo-yo effect’ and it is exasperating, but now a team of scientists from the Federal Institute of Technology in Zurich (ETH Zurich) has found a possible explanation for this phenomenon that could help prevent it.
These Swiss researchers have shown that the problem would have its origin in epigenetics, a branch of genetics that is based on small chemical signals. While the genetic sequence evolves over time and we inherit it from our parents, epigenetic marks are more dynamic and environmental factors and our lifestyle – such as dietary habits – or our physical condition – such as being overweight or obese – can modify them throughout life.
Although these marks are changeable, they can also remain stable for years, or even decades, determining which genes are active or inactive in our cells. “Epigenetics tells a cell what type of cell it is and what it should do,” explained Laura Hinte, a doctoral student in the group led by Ferdinand von Meyenn, professor of Nutrition and Metabolic Epigenetics, in an article published by ETH Zurich. .
Cells that remember obesity and contribute to the rebound effect
von Meyenn’s team, along with Daniel Castellano Castillo, a former postdoctoral researcher in his group, studied the molecular causes of the yo-yo effect in mice. They analyzed fat cells from overweight mice and those who had lost weight through diets and found that obesity generates characteristic epigenetic changes in the nuclei of fat cells and that these changes persist even after weight loss.
“Fat cells remember the overweight state and can return to that state more easily,” says von Meyenn. The researchers were able to show that mice with these epigenetic markers regained weight more quickly when they again had access to a high-fat diet. “That means we have found a molecular basis for the yo-yo effect,” he adds.
They also found evidence of this mechanism in humans. They analyzed biopsies of fatty tissue from people who had been obese and had undergone stomach reduction or gastric bypass surgeries. These samples came from studies conducted at the Karolinska Institute in Stockholm and hospitals in Leipzig, Dresden and Karlsruhe, and revealed gene expression patterns consistent with findings in mice. The results have been published in the journal Nature.
“Fat cells remember the overweight state and can return to that state more easily, which means we have found a molecular basis for the yo-yo effect.”
One question that researchers have not yet resolved is how long fat cells can remember obesity, since, according to Hinte, “fat cells have a long lifespan of an average of ten years before our body replaces them.” with new cells.”
Currently, it is not possible to modify these epigenetic marks in the cell nucleus using drugs to erase epigenetic memory. “Maybe in the future we will be able to do it,” says Hinte, “but for the moment we have to live with this memory effect.” Von Meyenn adds that “it is precisely because of this memory effect that it is so important to avoid being overweight, since that is the simplest way to combat the yo-yo phenomenon,” a message that she addresses especially to children and young people.
Research by ETH experts has shown for the first time that fat cells have an epigenetic memory of obesity, but they suspect that they are not the only cells with this capacity. “Other cells in the body could also play a role in the yo-yo effect,” says von Meyenn. It is likely that cells in the brain, blood vessels or other organs also remember obesity and contribute to the yo-yo effect, von Meyenn concludes. Future studies will seek to confirm this hypothesis.
