A study from ETH Zurich reveals a new insight into the yo-yo effect: fat cells have a memory linked to epigenetics.
Anyone who’s tried to lose some extra weight knows the disappointment: the pounds may drop off initially, but then they come back in just a few weeks—the classic yo-yo effect. Researchers at ETH Zurich have uncovered that this phenomenon is rooted in epigenetics.
Epigenetics refers to genetic factors that don’t involve the order of the DNA sequence but are instead influenced by small, unique chemical markers attached to the DNA. The actual sequence of these genetic building blocks has been passed down over generations, inherited from our parents. In contrast, epigenetic markers are more fluid: they can be altered by various factors, like environmental conditions, diet, and health status, including obesity, throughout a person’s life. Yet, they can remain unchanged for extended periods—sometimes even decades—during which they significantly impact which genes in our cells are active. “Epigenetics informs a cell about its identity and its functions,” explains Laura Hinte, a PhD student in Ferdinand von Meyenn’s lab, which specializes in nutrition and metabolic epigenetics.
Obesity’s epigenetic memory
The team of researchers, including Hinte and her colleague Daniel Castellano Castillo, investigated the biological reasons behind the yo-yo effect using mice. They examined fat cells from overweight mice and those that had lost weight through dieting. Their findings showed that obesity triggers notable epigenetic alterations in the cells’ nuclei. One crucial aspect of these changes is that they persist even after the mice have lost weight. “The fat cells retain a memory of the overweight condition and can revert back to it more easily,” notes von Meyenn. Furthermore, the team found that mice exhibiting these epigenetic markers quickly regained weight once they had access to a high-fat diet again. “This indicates we’ve identified a molecular foundation for the yo-yo effect.”
They also found supporting evidence in humans. The researchers analyzed fat tissue samples from previously overweight individuals who had undergone weight loss surgeries, such as gastric bypass. These samples came from multiple studies performed at Karolinska Institutet in Stockholm and various hospitals in Leipzig, Dresden, and Karlsruhe. Instead of focusing on epigenetic markers, they examined gene expression in these samples. The findings aligned with their observations in mice. Their research is detailed in the latest edition of the journal Nature.
Focus on Prevention
One area the researchers haven’t explored is how long fat cells can retain the memory of obesity. “Fat cells are long-lived, typically lasting around ten years before being replaced by new cells,” says Hinte.
At this point, it is not possible to alter the significant epigenetic markers in fat cell nuclei through medication to erase this memory. “This might be achievable in the future,” Hinte speculates. “But for now, we must contend with this memory effect.” Von Meyenn emphasizes: “This memory effect underscores the importance of preventing obesity in the first place. It remains the simplest strategy to mitigate the yo-yo phenomenon.” The researchers aim to convey this message particularly to children, young people, and their parents.
The ETH researchers have, for the first time, demonstrated that fat cells can retain an epigenetic memory of obesity. Nevertheless, they posit that fat cells may not be the only type of cells with such a memory. “Other cell types in the body may also contribute to the yo-yo effect,” von Meyenn suggests. It’s plausible that cells in the brain, blood vessels, or other organs also remember obesity and play a role in this process. Determining the validity of this assumption is the next step for the researchers.
