Fat Cells Retain a ‘Memory’ of Obesity, Making It Hard to Lose Weight and Keep It Off, Study Suggests

Fat cells have a “memory” of obesity, which may help explain why it’s so difficult to maintain weight loss, according to a new study published Monday in the journal Nature.

Individuals who have lost weight often later gain the weight back, in a phenomenon known as the “yo-yo effect.” Now, the new research suggests changes at the cellular level may be partially responsible for the body’s tendency to revert to obesity after weight loss.

Obesity leads to epigenetic changes, or chemical alterations to DNA that affect gene activity. The new paper suggests that in fat cells, these changes linger even after a person loses weight. And the cells, beyond simply “remembering” their prior state of obesity, “likely aim to return to this state,” says study co-author Ferdinand von Meyenn, an epigeneticist at ETH Zürich, to the Guardian’s Ian Sample.

Scientists studied body fat, also known as adipose tissue, from two groups of participants: One group had never been obese, while the other group had experienced severe obesity. When the researchers compared fat cells between the two groups, they found differences in gene activity.

Certain genes in the fat cells of participants with obesity were more active, and others were less active, compared to the control group, reports Nature News’ Traci Watson. The genes that were more active play a role in the formation of thick, scar-like tissue (called fibrosis), as well as inflammation. The genes that were less active are responsible for helping the fat cells function normally.

These gene activity patterns remained constant, even after the individuals with severe obesity had undergone weight-loss surgeries. Though the participants had lost weight, the genes in their fat cells still behaved as if they were obese.

The new results “show what’s happening at the molecular level, and that’s really cool,” Hyun Cheol Roh, an epigenome specialist at Indiana University School of Medicine who was not involved with the research, tells Nature News.

Next, researchers found similar epigenetic changes to fat cells in mice. In another experiment, they put obese mice on a diet. Once the mice had lost weight, researchers fed them a high-fat diet for one month; they also fed the same high-fat diet to mice that had never been obese.

The mice that had never been obese gained an average of 5 grams, while the previously obese mice gained an average of 14 grams, writes New Scientist’s Carissa Wong. When grown in a lab dish, the fat cells from the previously obese mice also absorbed more sugar and fat.

“From an evolutionary perspective, this makes sense,” says study co-author Laura C. Hinte, an epigeneticist at ETH Zürich, to the Guardian. “Humans and other animals have adapted to defend their body weight rather than lose it, as food scarcity was historically a common challenge.”

For now, researchers haven’t proved that the epigenetic changes to fat cells cause weight gain—they’ve only shown a correlation. In addition, epigenetic changes likely aren’t solely responsible for weight gain. Other factors are probably at play as well, such as the difficulty of maintaining a low-calorie diet for a long period of time.

Scientists are also not sure whether the obesity-linked epigenetic changes are permanent. And, if these DNA changes are reversible, researchers don’t know how long they last. But the findings suggest preventing obesity in the first place is likely easier than trying to lose weight and keep it off.

The knowledge that fat cells “remember” obesity could help doctors and public health experts design more effective weight-loss programs. Pharmaceutical companies could also one day develop new drugs that reverse the obesity-linked epigenetic changes, reports El País’ Jessica Mouzo.

More broadly, the findings could help reduce some of the stigma surrounding obesity.

“This is not just a lack of willingness or a lack of willpower, there’s really a molecular mechanism which fights against this weight loss,” von Meyenn says to Bloomberg’s Naomi Kresge.

Moving forward, the team wants to study other types of tissue, such as in the pancreas, liver and brain, to see whether their cells also have a “memory” of obesity. They also want to explore whether exercise or weight-loss drugs like semaglutide can affect the epigenetic changes linked with obesity.

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Sarah Kuta is a writer and editor based in Longmont, Colorado. She covers history, science, travel, food and beverage, sustainability, economics and other topics.