Anyone who has ever tried to get rid of a few extra kilos understands the frustration: The first few times you drop the weight it’s only temporary, with the “yo-yo effect” taking hold. The part of genetics that is based not on the sequence of genetic building blocks, but on small characteristics through chemical markers on these building blocks is called epigenetics.
Epigenetic markers, on the other hand, are more dynamic: These additives can be tweaked over your lifetime depending on environmental factors and the state of your body, for example, obesity. “Epigenetics essentially instructs a cell: ‘You are this type of cell and should perform this function, not that,'” explains Laura Hinte, a doctoral student in Professor Ferdinand von Meyenn’s group (Nutrition and Metabolic Epigenetics). Their findings were recently published in Nature.
In search of the molecular causes of the yo-yo effect, Hinte and his colleagues, including independent researcher Daniel Castellano Castillo, a former postdoc in von Meyenn’s group, turned their gaze to mice. And so, they looked at fat cells taken from overweight mice and those that had lost their excess weight on a diet. Obesity, they found, triggers characteristic changes in the fat cells nucleus. The particular change is that they persist even after a diet.
“When you gain weight, fat cells ‘remember’ and can revert to this state more easily,” von Meyenn explains. The researchers demonstrated that when mice with these epigenetic markers were reintroduced to a high-fat diet, they regained weight more rapidly. “This provides molecular evidence for the yo-yo effect,” he adds.
They also observed similar findings in humans. The ETH Zurich researchers analyzed fat tissue biopsies from formerly obese individuals who had undergone stomach reduction or gastric bypass surgery. However, the study did not determine how long fat cells retain their memory of obesity.
‘Fat cells are long-lived cells.’ That’s why they are in our body for only 10 years on average and are then replaced by new cells, Hinte says. What’s more, currently available drugs can’t even change the epigenetic mark relevant for erasing the cell nucleus’ epigenetic memory.
“Hence, for now, we have to ‘live with this memory effect.’ However, von Meyenn writes that this memory effect makes it an important reason to prevent one’s ever becoming overweight to start with, as this is the easiest way to sidestep the yo-yo syndrome.”
The ETH researchers have shown for the first time that fat cells have an epigenetic memory of obesity with their work. But they don’t assume that only fat cells are capable of such a memory. Von Meyenn also suggests that other body cells could have a hand in the yo-yo effect. Another possibility is that cells in the brain, blood vessels, or elsewhere in the body remember obesity and play a role in that.
Reference: Hinte LC, Castellano-Castillo D, Ghosh A, et al. Adipose tissue retains an epigenetic memory of obesity after weight loss. Nature. Published online November 18, 2024. doi:10.1038/s41586-024-08165-7‌
