Why is it so easy to regain weight after losing it? New research sheds light on the 'yo-yo effect'

Many people who diet and lose a significant amount of weight know the devastation of gaining most – or all of it – back within a short amount of time. This phenomenon is often referred to as the "yo-yo effect," or "yo-yo dieting." Millions of Americans try to lose weight every year.

And yet, more than 40% of U.S. adults 20 and older have obesity , a chronic condition linked to serious health risks , including cardiovascular disease, type 2 diabetes and some cancers.



Even the advent of popular weight loss drugs hasn't diminished the yo-yo effect. One year after stopping semaglutide injections, people regained two-thirds of the weight they had lost, according to a 2022 study. Similarly, research from 2023 found that people who withdrew from tirzepatide regained a substantial amount of weight.

Semaglutide is the drug in Ozempic and Wegovy; tirzepatide is the drug in Zepbound and Mounjaro. Yo-yoing occurs partly because when people typically lose some muscle when they rapidly lose a significant amount of weight. Extreme dieting also can slow the metabolism .

But a study published Monday in Nature has revealed a possible molecular cause of the yo-yo effect: cells retain a "memory" of obesity after weight is lost, making it more likely for people to put weight back on. By analyzing fat cells in mice who lost weight and then regained it when they were exposed to a high-fat diet, researchers from ETH Zurich in Switzerland found that there were changes in the nucleus of the cells. "The fat cells remember the overweight state and can return to this state more easily," said Ferdinand von Meyenn, a professor of nutrition and metabolic epigenetics who led the study.

​​ "...

It's precisely because of this memory effect that it's so important to avoid being overweight in the first place." The researchers also analyzed fat tissue biopsies from formerly overweight people who had had gastric bypass or other forms of weight-loss surgery, finding outcomes consistent with those with the mouse experiments. The next step is to look at whether weight loss drugs, exercise and other factors affect how cells store memories of fat, the researchers said.

.