Scientifically Speaking: Fat cell memory might contribute to weight regain

The findings raise questions about the long-term effectiveness of obesity treatment with GLP-1 receptor drugs after initial weight loss

If losing weight feels like an uphill battle, keeping it off seems even harder. I’m one of the countless people who’ve experienced the yo-yo effect of regaining the weight I had lost after loosening my diet.

Now, new research shows that losing weight isn’t just about counting calories or willpower; our bodies seem to work against us. (Representative file photo)

Now, new research shows that losing weight isn’t just about counting calories or willpower; our bodies seem to work against us. Professor Ferdinand von Meyenn and his team at ETH Zurich report in Nature that fat cells retain a “memory” of past obesity, making it easier to regain weight after earlier weight loss.

This striking discovery comes from the biological field of epigenetics, which explores how the environment and our lifestyles leave chemical “tags” on our DNA. These tags can change based on factors like diet, exercise, and health conditions such as obesity. This helps to determine how our genes are turned on or off, guiding cells to perform specific roles. As von Meyenn explains, “Epigenetics tells a cell what kind of cell it is and what it should do.”

Von Meyenn’s team sought to understand if epigenetic changes could explain the yo-yo effect. They studied fat tissue from mice and humans. In mice, they induced obesity by feeding these rodents a high-fat diet, then switched to a standard diet to mimic weight loss. Human data came from individuals who had undergone bariatric surgery, which typically results in dramatic weight loss. In both cases, they found that fat cells retained attributes linked to obesity even after weight loss.

The researchers also analysed gene activity in fat cells. They found that obesity altered genes associated with inflammation, tissue scarring, and fat storage. Remarkably, even after weight loss, these genes remained in a state that caused fat cells to behave as though the body were still obese. In mice, this memory led to faster weight regain when they returned to a high-fat diet compared to mice that had never been obese.

In humans, the study primarily examined gene expression rather than directly analysing epigenetic markers, making the connection between memory and weight regain less definitive than in mice. However, the patterns in gene activity were similar to those observed in mice, which means that a similar process is probably at work in people too.

This research offers a biological explanation for why maintaining weight loss can be so challenging, even with healthy habits. Fat cells in formerly obese individuals behave differently, storing more fat and burning it less efficiently than those in people who have never been obese.

Other studies support these findings. After weight loss, the body tends to burn fewer calories at rest and increases levels of ghrelin, the hunger-stimulating hormone. Together with the epigenetic changes in fat cells, it’s clear that multiple biological mechanisms make weight gain more likely in people who have lost a lot of weight.

The most obvious implication of this work lies in the importance of prevention as a long-term strategy for tackling obesity. Von Meyenn stresses, “Because of this memory effect, it’s so important to avoid being overweight in the first place.”

Fat cells live for about 10 years, so this memory could influence metabolism for a long time, highlighting the need to promote healthy eating and active lifestyles early in life, especially for children and teenagers.

The findings raise questions about the long-term effectiveness of obesity treatments, such as GLP-1 receptor drugs like Ozempic, Wegovy, and Zepbound after an initial weight loss. These medications, which mimic a hormone that regulates appetite and blood sugar, have shown impressive results in helping people lose weight. However, many patients regain the weight after stopping the drugs. It’s currently unclear if people who lost a lot of weight taking GLP-1 drugs need to stay on these drugs their whole lives to retain the full benefit.

Obviously, this doesn’t mean that anyone who has gained weight won’t be able to keep it off, but rather that the balance might be tilted against them. It’s also worth noting also that the human studies were done in individuals who were obese and had surgery, and so the results might not be as pronounced for others.