Anyone who has ever tried to get rid of a few extra kilos knows the frustration: the weight drops initially, only to be back within a matter of weeks – the yo-yo effect has struck. Researchers headed by ETH Zurich have now been able to show that this is all down to epigenetics. Epigenetics is the part of genetics that’s based not on the sequence of genetic building blocks but on small yet characteristic chemical markers on these building blocks. The sequence of building blocks has evolved over a long period of time; we all inherit it from our parents. Epigenetic markers, on the other hand, are more dynamic: environmental factors, our eating habits and the condition of our body – such as our weight – can change them over the course of our lives. But they can remain stable for many years, sometimes decades, and during this time, they play a key role in determining which genes are active in our cells and which are not.
Epigenetic memory of obesity
The researchers looked for the molecular causes of the yo-yo effect in mice. They analysed fat cells from overweight mice and those that had shed their excess weight through dieting. Their investigations revealed that obesity leads to characteristic epigenetic changes in the nucleus of fat cells. What’s special about these changes is that they remain even after a diet. The scientists were able to show that mice with these epigenetic markers regained weight more quickly when they again had access to a high-fat diet.
They also found evidence for this mechanism in humans. The researchers analysed fat tissue biopsies from formerly overweight people who had undergone stomach reduction or gastric bypass surgery. The tissue samples came from various studies carried out at Karolinska Institutet in Stockholm and at the University of Leipzig Medical Center. In these samples, the researchers analysed gene expression rather than epigenetic markers. However, the results are consistent with those of the mice.
Prevention is key
It’s not currently possible to change the relevant epigenetic marks in the cell nucleus with drugs and thus erase the epigenetic memory. “It is because of the memory effect that it is so important to avoid being overweight in the first place. It is probably easier to prevent an unfavourable epigenetic memory than to reverse it once obesity has developed,” says Professor Matthias Blüher, Professor of Clinical Obesity at the University of Leipzig Medical Center and co-author of the study.
With their work, the researchers have shown for the first time that fat cells possess an epigenetic memory of obesity. However, they don’t assume that fat cells are the only cells with such a memory. It’s quite conceivable that cells in the brain, blood vessels or other organs also remember obesity and contribute to the effect.
Original publication in Nature:
“Adipose tissue retains an epigenetic memory of obesity that persists after weight loss”, doi: 10.1038/s41586-024- 08165-7