The so-called “yo-yo effect” is well-known to anyone trying to lose weight: after every successful diet, those hard-lost kilos always seem to come back. But this vicious circle might not just be down to lack of willpower – instead, it could also be owing to the epigenetic memory of fat cells, according to a study published in the Nature journal.
An international research team led by professor Ferdinand von Meyenn of ETH Zurich set out to understand the molecular causes of the yo-yo effect. They analysed fat cells from obese mice, as well as those from mice that had lost weight after dieting.
Their findings revealed specific epigenetic modifications due to obesity – chemical changes that dictate how genes are expressed in the nucleus of fat cells, without affecting the DNA itself. These alterations persist after weight loss, as if fat cells “retained memory” of this past obesity. As a result, these cells tend to quickly return to their previous state when re-exposed to a high-fat diet.
The results observed in mice were also verified in humans: analyses of fat tissue from formerly overweight people who had undergone stomach reduction or gastric bypass surgery revealed striking similarities in gene expression.
In other words, our fat cells do indeed possess a memory of obesity, which could explain why formerly obese people may have a greater propensity to put on weight than individuals with no history of obesity, despite having a similar diet.
At present, no pharmacological solution can erase the epigenetic marks of obesity. “Maybe that’s something we’ll be able to do in the future. But for the time being, we have to live with this memory effect,” study co-author Laura Hinte said.
The researchers stress the importance of a healthy diet and regular exercise from an early age to prevent obesity. “It’s precisely because of this memory effect that it’s so important to avoid being overweight in the first place. That’s the simplest way to combat the yo-yo phenomenon,” von Meyenn noted.
It remains to be seen whether fat cells are the only ones to retain traces of obesity. The researchers believe that this epigenetic memory could extend to other cell types, such as those of the brain or blood vessels, which could explain why it is so difficult to maintain a stable weight after a weight-loss programme.
Still, it’s not impossible: von Meyenn and his team suggest that there may be a window during which the body can erase the epigenetic memory of obesity – an encouraging hypothesis for anyone trying to lose weight and keep it off for good.