The challenge of keeping weight off after losing it has puzzled many people working to improve their health. While shedding extra pounds can have clear benefits, many find themselves gaining the weight back despite maintaining healthier habits. A new study, led by Professor Ferdinand von Meyenn from ETH Zurich and published in Nature, offers an explanation: fat cells seem to remember obesity, making it harder to keep the weight off long-term.
Professor von Meyenn’s team examined fat tissue, the body’s energy-storing cells, from both humans and mice before and after significant weight loss. They discovered that even after people and animals lost weight, their fat cells retained certain biological changes linked to obesity. In mice, these changes also affected how fat cells functioned and responded to food, altering their ability to store and burn energy efficiently. “Our findings indicate that fat cells hold onto a memory of obesity, which makes it easier to regain weight after dieting,” explained Professor von Meyenn.
The study showed that mice with a history of obesity put on weight faster when they returned to a high-fat diet, compared to those that had never been obese. Their fat cells had lasting changes that affected how genes, the instructions that tell cells what to do, were turned on and off, making it harder for them to regulate metabolism, the body’s process of converting food into energy, normally. This suggests that fat tissue doesn’t just shrink when weight is lost; it remains biologically altered in a way that influences future weight gain.
One of the biggest takeaways from this research is how weight regain may be linked to changes in the way fat cells function, rather than just lifestyle habits. Unlike permanent genetic mutations, which are changes in the DNA sequence itself, these changes—called epigenetic modifications, chemical markers that control gene activity without altering DNA—can still influence how cells behave. “These changes seem to prepare fat cells to respond more strongly to unhealthy food, which may explain the common ‘yo-yo’ effect, where lost weight is regained after dieting,” said Professor von Meyenn. This suggests that past obesity leaves a long-term imprint, making it harder to maintain weight loss.
While most weight loss strategies focus on diet and exercise, this research suggests that a deeper, biological factor may be at play. If scientists can find a way to reset this fat cell memory by modifying epigenetic markers, it could lead to better treatments for maintaining weight loss. Future therapies may aim to reverse these changes, helping people keep the weight off more effectively and reducing the risk of obesity-related diseases such as diabetes and heart disease.
This study not only improves our understanding of obesity but also highlights the need for new ways to support long-term weight management. By recognizing that fat cells have a biological memory, researchers may be able to develop treatments that make it easier for people to maintain a healthy weight in the long run.
Journal Reference
Hinte, L.C., Castellano-Castillo, D., Ghosh, A., et al. “Adipose tissue retains an epigenetic memory of obesity after weight loss.” Nature, 2024. DOI: https://doi.org/10.1038/s41586-024-08165-7
About the Author
Professor Ferdinand von Meyenn is a leading expert in epigenetics and metabolic research, with a focus on how environmental factors shape gene activity and influence health. He is a professor at ETH Zurich, where his work explores the long-term molecular effects of diet, obesity, and aging on the body. His research has been instrumental in uncovering how fat cells retain a biological memory of obesity, contributing to challenges in long-term weight loss.
With a strong background in molecular biology and genetics, Professor von Meyenn has published extensively in high-impact scientific journals. His laboratory uses advanced techniques such as single-cell sequencing and epigenomic profiling to investigate how cells regulate metabolism over time. Passionate about translational science, he aims to develop strategies that could lead to new treatments for obesity-related diseases. Through his work, he continues to shape the future of metabolic and genetic research.
