Gaining weight quickly after losing it? Scientists may have found the answer

A new study published in Nature suggests that even after pounds are shed, fat cells hold on to a kind of “memory” that makes it harder to stay slim and healthy.

This new research, led by a team of Swiss scientists, points to fat cells as a key driver of this rebound effect. The study found that fat cells influence abnormal metabolic pathways in the body long after someone has lost weight, making it easier for those pounds to come back.

Investigating “Metabolic Memory”
The scientists explored the idea of “metabolic memory,” where the body seems to recall its obese state and tries to return to it. They tested this in mice fed a high-fat diet that became obese. Once these mice lost weight on a standard diet, the researchers analyzed chemical markers on their fat cells to see if they were tied to unhealthy metabolic changes.

The study revealed that even after significant weight loss, these formerly obese mice still carried fat cells with persistent changes that triggered more inflammation, poorer sugar control, and abnormal fat storage.


When the mice resumed a high-fat diet, they regained weight much faster than lean mice—strong evidence that this “memory” continued to disrupt metabolism.

The researchers also analyzed fat tissues from people who had undergone bariatric surgery, comparing them to lean individuals who had never been obese. Two years after weight loss, the fat cells of those who were formerly obese still showed abnormal activity—more inflammation and metabolic dysfunction—highlighting how deeply this memory is embedded.

What is the epigenetic link?
According to the study’s findings, this “obesogenic memory” is driven by changes in how genes work, known as epigenetics. These changes rather than altering the genetic code itself, shift how genes function and respond to future high-fat diets. In both mice and humans, these epigenetic changes in fat cells seem to prime the body to regain weight quickly and keep it off only with great difficulty.


The researchers concluded that this cellular memory might explain why so many people experience the frustrating cycle of losing and regaining weight—often called “yo-yo dieting.” They believe that in the future, targeting these epigenetic changes in fat cells could help people keep weight off for good.

However, the researchers only looked at fat cells. More research is needed to see if other cells or tissues in the body also keep a memory of obesity.