Brown fat tissue burns calories rather than storing them (Photo by Towfiqu Barbhuiya on Unsplash)
ZÜRICH, Switzerland — If you’ve ever lost weight only to watch the pounds creep back on, you’re not alone. Now, scientists have uncovered a biological explanation for this frustrating phenomenon known as the “yo-yo effect” – and it turns out our fat cells have a surprisingly long memory.
Researchers at ETH Zurich have discovered that being overweight leaves a lasting imprint on our fat cells through a process called epigenetics – chemical markers that act like tiny switches controlling which genes are turned on or off in our cells. These markers can persist for years, making it easier for the body to regain weight even after successful dieting.
“The fat cells remember the overweight state and can return to this state more easily,” explains Professor Ferdinand von Meyenn, who led the study published in Nature.
To reach this conclusion, the research team first studied mice, examining fat cells from both overweight mice and those that had successfully lost weight through dieting. They found that obesity created distinctive epigenetic “stamps” on the fat cells that stubbornly remained even after weight loss. When these mice were later given access to high-fat foods, they regained weight more quickly than mice without these cellular memories.
The findings weren’t limited to mice. The team also analyzed fat tissue samples from formerly overweight people who had undergone weight loss surgery, using samples from medical centers in Sweden and Germany. While they looked at different cellular markers in the human samples, the results aligned with their mouse studies, suggesting that human fat cells also “remember” their previous size. Perhaps most striking is how long this cellular memory might last.
“Fat cells are long-lived cells. On average, they live for ten years before our body replaces them with new cells,” says Laura Hinte, a doctoral student involved in the research.
Currently, there’s no way to erase these cellular memories with medication, though that could change in the future. For now, the researchers emphasize that prevention is key, particularly for young people.
“It’s precisely because of this memory effect that it’s so important to avoid being overweight in the first place. Because that’s the simplest way to combat the yo-yo phenomenon,” von Meyenn notes.
The team is now investigating whether other types of cells, such as those in the brain or blood vessels, might also harbor memories of previous weight gain. If so, this could help explain why maintaining weight loss is such a complex challenge for so many people.
This breakthrough research not only helps explain a frustrating aspect of weight loss that millions have experienced but also underscores the importance of preventing weight gain in the first place – our cells, it seems, never quite forget.
Paper Summary
Methodology
This study investigated how the body “remembers” obesity, even after significant weight loss. Researchers analyzed human and mouse fat tissues before and after weight loss, focusing on how cells in these tissues change at the molecular level. Advanced techniques, like single-nucleus RNA sequencing, were used to zoom in on individual cells and see how their behavior changed.
In mice, researchers also studied how these changes impacted future weight gain after a high-fat diet. To dig deeper, they looked at the epigenetic “instructions” that control how fat cells function, identifying patterns that might explain why the body seems primed to regain weight.
Key Results
The study found that both human and mouse fat tissues keep a “memory” of obesity. Even after weight loss, certain genes in fat cells stayed active or inactive in ways that made the cells less efficient. This “obesogenic memory” made it easier for the body to gain weight again.
For example, mice that lost weight regained it faster when put back on a high-fat diet compared to mice that were never obese. This suggests that weight loss doesn’t erase the body’s history of obesity—it leaves behind molecular traces that influence future weight and health.
Study Limitations
In humans, researchers could only analyze fat tissue from individuals who had bariatric surgery, which might not represent all forms of weight loss. Additionally, the molecular changes in mice may not perfectly match those in humans. The study also couldn’t confirm whether these epigenetic changes directly cause the “yo-yo” effect or if they’re just one piece of a larger puzzle.
Discussion & Takeaways
The research highlights a critical challenge in obesity treatment: even after significant weight loss, the body’s fat cells seem primed for weight regain. This discovery suggests that long-term weight management may require treatments targeting these persistent molecular changes. Future therapies might involve altering the epigenetic markers in fat cells to “erase” the memory of obesity. For now, the findings emphasize the importance of continuous lifestyle and dietary management after weight loss.
Funding & Disclosures
This study was supported by the Swiss Federal Institute of Technology Zurich (ETH Zurich), which also provided open-access funding for publication. The research involved contributions from multiple institutions, reflecting a collaborative effort across international research centers. Authors affiliated with ETH Zurich and the Functional Genomics Center Zurich contributed to the study’s experimental design, data analysis, and human sample collection.
Researcher Matthias Blüher received honoraria for consulting and speaking engagements with several pharmaceutical companies, including Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Lilly, Novo Nordisk, and Sanofi. Researcher Mikael Rydén also received honoraria for similar roles with AstraZeneca, Boehringer-Ingelheim, Lilly, Novo Nordisk, and Sanofi. No other authors reported conflicts of interest.
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