Yo-yo of weight gain and loss explained

Researchers from Switzerland have discovered a mechanism behind the yo-yo effect: fat cells have a memory that is based on 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 which we inherit from our parents. Epigenetic markers are based on environmental factors, our eating habits and the condition of our body such as obesity. They may change during your lifetime. But can also 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.

Researchers at the Federal Institute of Technology Zurich in Switzerland studied the molecular causes of the weight gain after dieting in mice. They analysed fat cells from overweight mice and those that had shed their excess weight through dieting. The study revealed that obesity leads to characteristic epigenetic changes in the nucleus of fat cells. These changes remain even after a diet - the fat cells do not forget the overweight state and can return to this state more easily. 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. This established that there was a molecular basis for the weight which was regained after dieting.

The researchers also studied fat tissue collected from 20 people with obesity just before they had bariatric surgery and again two years later, when they had lost at least a quarter of their initial body weight. They also looked at fat tissue from 18 people with a healthy weight. The tissue samples came from various studies carried out at Karolinska Institute in Stockholm and at hospitals in Leipzig, Dresden and Karlsruhe. In these samples, the researchers analysed gene expression rather than epigenetic markers. However, the results are consistent with those of the mice.

This research study has shown for the first time that fat cells possess an epigenetic memory of obesity. The researchers stressed that what needs to be further studied is if that cells in the brain, blood vessels or other organs also remember obesity and contribute to weight gain.

Source: Nature 2024