| Almost anyone who has ever been on a diet will be well aware of the unrelenting and dispiriting yo-yo effect of losing and then regaining weight. And while weight-loss drugs like Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound have taken the world by storm, the rebound happens here too, as soon as most people stop taking the shots. Patients in two of Novo’s clinical trials regained most of the weight they’d lost within a year after stopping the medicine. A study of Zepbound also showed substantial weight regained. The reason why this happens may lie within cells themselves, research published on Monday in Nature revealed. Fat cells have a “memory” of obesity that lingers even after weight is lost, a team from ETH Zurich and other universities showed in a study in human and mouse cells. Their research found changes in the way the cells use the genetic information to carry instructions, in particular about the chemical reactions that govern how cells process energy. The results show that cells adapt to obesity — and these changes in function at the cellular level seem to remain even after weight is lost, says Ferdinand von Meyenn, an assistant professor of nutrition and metabolic epigenetics at ETH Zurich, who led the research. “Metabolically many processes will be rewired,” Von Meyenn says. “The cells adapt to that stimulus. We take the stimulus away, and the cells still retain that memory.” It’s still healthy to lose weight, Von Meyenn says. But the results help explain why the body pushes so hard to regain weight after it’s lost. One hypothesis is that exercise — essentially giving the body another type of stimulus — could help reprogram the cells’ memory, he says, though that is unproven. The Swiss team now wants to study whether exercise and drugs like Novo’s Ozempic could help change the cellular memory of fat, Von Meyenn says. Scientists are also interested in whether the cell memory only lies in fat tissue or whether other organs such as the brain, liver and pancreas could be involved. “Prevention is key,” he says. “If you never have been obese, you will never be exposed to that memory and never have this problem of regaining weight.” And importantly, the results also show that people shouldn’t be stigmatized for regaining weight, he says. “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.” — Naomi Kresge | 
