We're starting to understand why some people regain weight they lost

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People with obesity who lose weight often put it back on, which may partly be driven by lasting changes to the DNA within their fat cells, a discovery that could one day lead to new treatments.

Around 85 per cent of people with overweight or obesity who lose at least a tenth of their body weight regain it within a year.

That is partly because it is hard to maintain low-calorie diets for a long period of time, though that probably plays a relatively small role, says Laura Catharina Hinte at the Federal Institute of Technology Zurich in Switzerland. “It can’t be that we all don’t have enough willpower to maintain lost weight.”

Studies have also shown that the brain interprets a sharp drop in body fat as dangerous and responds by making the body burn less energy.

To learn more about this process, Hinte and her colleagues analysed fat tissue collected from 20 people with obesity just before they had bariatric surgery, which shrinks the stomach to make people feel fuller sooner, and again two years later, when they had lost at least a quarter of their initial body weight. They also looked at fat tissue from 18 people with a healthy weight.

The researchers sequenced a type of genetic molecule called RNA, which encodes proteins, in fat cells. They found that people with obesity had increased or decreased levels of more than 100 RNA molecules compared with people of a healthy weight, and these differences persisted at two years after weight loss.

These changes seem to ramp up inflammation and disrupt how fat cells store and burn fat, both of which raise the risk of future weight gain, says team member Ferdinand von Meyenn, also at the Federal Institute of Technology Zurich.

To explore whether these RNA changes might drive rebound weight gain, the researchers first confirmed that similar changes persisted after obese mice lost weight. They then fed these mice and mice of a healthy weight a high-fat diet for one month. While the previously obese mice gained 14 grams of weight, on average, the other mice gained just 5 grams.

The team also found that fat cells from the previously obese mice took up more fat and sugar when grown in a lab dish than those from the other mice. Together, the results show how obesity-linked RNA changes may increase future weight gain, says von Meyenn.

Finally, the team found that molecular tags, or epigenetic marks, on DNA in the fat cells seemed to drive the obesity-linked RNA changes. These alter RNA levels by changing the structure of the DNA that encodes them.

While the study didn’t look for these molecular tags in the people they studied, or examine whether they regained the weight they lost, the findings probably translate from mice to humans, says Henriette Kirchner at the University of Lübeck in Germany.

This is based on similarities between the physiology of these species and how the environment can change the way their genes work, known as epigenetics, she says. In the decades to come, drugs that target epigenetics could help treat obesity, says Kirchner.

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