Fat cell memories: Why it's hard to maintain healthy weight

Keeping weight off can be hard. Often it feels like you're fighting with your body to keep the weight off after months of successful dieting and exercise.

A new study has discovered why — and it's all down to fat cell "memories." The research, published in the journal Nature, found that fat cells have a kind of biological memory of past obesity and strive to return to this state.

The study found that it wasn't the number of fat cells that change when a person gains weight, but rather how existing fat cells store nutrients.

This "obesity memory" can last for years after a person has lost weight, making them more prone to gain weight again.

"Our study indicates one reason why maintaining body weight after initial weight loss is difficult. It means that one would have to 'fight' this memory to maintain body weight," said Ferdinand von Meyenn, a co-author of the study, who heads a group at the Institute of Food, Nutrition and Health, ETH Zurich, Switzerland.

Yo-yo effect of weight gain due to fat cells

The researchers discovered these "fat cell memories" by examining fat tissue taken from people with obesity before and after undergoing weight-loss surgery. They compared this fat tissue with individuals who had no history of obesity.

Some genes were more active in the obesity group's fat cells than in the control group. These genetic changes lasted long after their weight-reduction surgery.

This led the researchers to find that the molecular memory in fat cells was due to epigenetic changes to the genome.

Epigenetic changes occur when gene expression is altered by our environment — meaning that rapid weight gain isn't necessarily inherited, but can also be a result of events we experience in life.

Memory-primed fat cells store nutrients differently

Additional research by the group found that fat cells from obese mice responded to food differently than cells from non-obese mice.

"In mice, we observed that formerly obese mice regain weight faster when presented with a high caloric diet. In humans we have found indirect evidence of this kind of memory as well," said the study's co-author Laura Hinte, an expert in nutrition and metabolic epigenetics at ETH Zurich.

This suggests that the memory of obesity primed these fat cells to get larger faster and to take up more nutrients.

Penny Ward, a physician at Kings College London, UK, commented: "This explains why many people notice that it takes a shorter time to put the weight back on after they stop dieting than before they got fat in the first place."

The scientists in Zurich also tried putting mice on a diet to reduce their weight. They found that this obesity memory persisted, and that these mice gained weight again more rapidly than the mice in the control group.

"This memory seems to prepare cells to respond quicker to a [high sugar or high-fat food] environment, which could be linked to regain of body weight after a diet," von Meyenn told DW.

Fighting against evolutionary bias towards weight gain

The authors said it's likely that other factors elsewhere in the body also contribute to the yo-yo effect of weight loss and weight gain.

"An [obesity] memory in fat cells does not explain the accelerated weight gain alone," said von Meyenn. "If similar mechanisms exist in brain cells, which control food intake, for example, this could help explain the yo-yo effect seen in weight regain."

This makes sense from an evolutionary perspective, von Meyenn said. Humans and other animals have adapted to defend their body weight rather than lose it, as food scarcity has been a common and reoccurring challenge, historically.

"On a societal level, this could offer some solace to individuals struggling with obesity, as it suggests that the difficulty in maintaining weight loss may not be due solely to a lack of willpower or motivation, but rather to a deeper cellular memory that actively resists change," said von Meyenn.

How long do fat cell memories last?

The study authors said it was possible that fat cell memory fades with time but that it was unclear how long this takes.

"In the timespan we looked at — 2 years in humans and 8 weeks in mice — we still found changes that persisted in cells of the adipose tissue. It is possible that these will be erased over a longer period of weight maintenance," Hinte told DW.

Human fat cells live for around 10 years, which means it could take 10 years for the obesity memory in cells to vanish. 

Currently, there are no pharmacological interventions that could cause fat cells to "forget" their bias towards nutrient storage. 

Ward said it may be possible in the future to reprogram adipose tissue so that weight is not regained once subjects end a diet or stop taking weight-loss medication.

"That said, it is still a long way to move towards using these observations to then invent and test potential treatments to deprogram these changes," Ward told DW.

It is possible that maintaining a reduced or healthy body weight for long enough is enough to erase the memory, but Ward added, this needs further research.

Edited by: Zulfikar Abbany

Primary source:

Adipose tissue retains an epigenetic memory of obesity after weight loss; study published by Hinte, L.C., Castellano-Castillo, D., Ghosh, A. et al. in the journal Nature (November 2024). https://doi.org/10.1038/s41586-024-08165-7