Fat ‘remembering’ past obesity drives yo-yo diet effect, say experts

Losing weight can be a frustrating game: after months of successful slimming, the kilos may soon pile on again, leaving people back where they started.

No one factor drives the yo-yo effect, but new research points to fatty tissue as a leading culprit. Fat “remembers” past obesity and resists attempts to lose weight, scientists found.

Researchers identified the biological memory after examining fat tissue from people with obesity before and after they lost weight after bariatric surgery. The tissues were further compared with fat from healthy individuals who had never been obese.

The analysis showed that fat cells were affected by obesity in a way that altered how they responded to food, potentially for years. In tests, the cells grew faster than others by absorbing nutrients more swiftly.

Prof Ferdinand von Meyenn, a senior author on the study at the Federal Institute of Technology in Zurich, said: “Our study indicates that one reason maintaining body weight after initial weight loss is difficult is that the fat cells remember their prior obese state and likely aim to return to this state.

“The memory seems to prepare cells to respond quicker, and maybe also in unhealthy ways, to sugars or fatty acids.”

Further work on mouse cells traced the biological memory to chemical modifications on DNA or the proteins DNA is wrapped around. These epigenetic changes alter gene activity and metabolism.

Writing in Nature, the scientists describe how formerly obese mice gained weight faster than others when put on a high-fat diet, suggesting a shift in metabolism that made it easier for them to gain weight. The memory of obesity in fat cells was not solely to blame, however. The scientists suspect a similar memory exists in brain cells that affects how much food animals consume and how much energy they expend.

Dr Laura Hinte, first author on the study, said: “From an evolutionary perspective, this makes sense. Humans and other animals have adapted to defend their body weight rather than lose it, as food scarcity was historically a common challenge.”

Nearly two-thirds of adults in England are overweight or living with obesity and globally the condition affects more than a billion people. Obesity costs the NHS £6.9bn a year and is the second-biggest preventable cause of cancer.

Another researcher, Dr Daniel Castellano-Castillo, said: “On a societal level, this could offer some solace to individuals struggling with obesity.” Struggling to keep the kilos off could be driven by a cellular memory that “actively resists change”, he said.

The work could pave the way for better weight management programmes, though the cellular memory of obesity may also fade with time. “It’s possible that maintaining a reduced or healthy body weight for long enough is enough to erase the memory,” said Hinte.

Prof Henriette Kirchner at the University of Lübeck called the finding “very plausible”. “I’m convinced it plays an important role in the yo-yo effect after dieting,” she said. “The researchers show convincingly that the memory becomes harder to erase the longer you were obese.”

People who lose weight through dieting or after weight-loss jabs such as Wegovy typically regain weight when they stop.

David Benton, a professor emeritus at Swansea University and author of the 2024 book Tackling the Obesity Crisis: Beyond Failed Approaches to Lasting Solutions, said more than 100 factors influenced obesity.

“Obesity reflects consuming more calories than you burn. When a diet removes energy you lose weight,” he said. “However, the mantra is that diets fail. They fail because to avoid regaining lost weight you need to permanently change your diet. Most often having finished the diet, we return to the lifestyle that caused the problem in the first instance. The result is yo-yo dieting.”