Obesity leaves a lasting imprint on fat and immune cells, which could make weight regain more difficult to avoid.
By Lori Youmshajekian edited by Lauren J. Young

Color scanning electron micrograph (SEM) of a sample of adipose tissue, showing fat cells (adipocytes).
STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY/Getty Images
Weight loss is notoriously difficult to maintain. Within a few years, most people regain the weight they initially lost, whether through follow a diet, exercise, surgery or weight loss medications such as popular glucagon-like peptide 1 (GLP-1) drugs. Recent research suggests that fat cell “memory” may explain why.
Fat-storing cells, or adipocytes, and immune cells, such as macrophages, that live in fatty tissue can remember weight long after it is lost. And scientists suggest that obesity causes lasting changes in these cells, making it easier for the body to return to an obese state, even after significant weight loss. The changes are engraved in the epigenome of cellsthe instructions that tell each cell to read specific genes that control its function, explains Ferdinand von Meyenn, who studies nutrition and metabolic epigenetics at the Swiss Federal Institute of Technology in Zurich. This ensures that a liver cell does not suddenly behave like a neuron, for example. In obese people, lasting epigenetic changes could cause the body to regain weight more easily if they consume more calories.
Von Meyenn’s team measured gene activity in individual cells with a technique called RNA sequencing to compare adipose tissue from obese people before their onset. bariatric surgery with similar tissues from non-obese people. Even after the obese participants lost about 25 percent of their body mass index after their surgery, some of their genes remained unbalanced. This suggests that some adipose tissues did not recover from obesity: some genes controlling metabolic function and inflammation remained abnormally activated or deactivated, for example, says von Meyenn.
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Previous studies have shown that fat cells in obese mice preserve epigenetic alterations even after the animals have lost weight. When then fed a high-fat diet, these mice regained weight more quickly than control animals. Laboratory tests showed that fat cells from obese mice absorbed glucose and lipids more easily. Fat cells normally absorb sugars and lipids, von Meyenn said, but these obesity-impaired cells appeared “slightly modified” to absorb more of these nutrients.
Other research groups have demonstrated that immune cells can also remember previous weight. When a person gains weight, different types of immune cells infiltrate the expanding fatty tissue, probably in response to stress, says William Scott, an obesity researcher at Imperial College London. His research showed that after bariatric surgery, the number of immune cells in people’s fatty tissues decreased significantly, but it didn’t completely reset. Immune cells retained the inflammatory characteristics which developed when people suffered from obesity.
Mouse research has echoed this finding; even after weight loss, macrophages retain epigenetic changes that keep inflammatory genes more active than usual. Another study in mice shows that weight cycling – losing and regaining weight – can intensify these changes in immune cells and worsen metabolic health more than ever to lose weight.
How long this epigenetic memory lasts is unclear, but fat cells can persist for up to a decade in humans, giving these cells the potential to maintain long-term changes, says von Meyenn. And fat may not be the only tissue involved. “I think changes are happening in the brain, in the liver and in the muscles,” says von Meyenn, who plans to study these areas in the future.
These results do not mean that weight loss is futile; Even short-term weight loss correlates with improved metabolic health. But the research could help explain why weight relapses are so common and why it’s important to avoid weight gain. In a environment And Company that promote weight gain, prevention is much easier said than done, says von Meyenn. Researchers, including von Meyenn, are currently studying whether fat cells can be treated to rewrite these epigenetic changes to make weight loss more sustainable and whether different types of weight loss interventions have different effects on these cells.
“There is a great desire to manufacture our weight-loss drugs [such as GLP-1 medications] more powerful” to result in greater weight reductions, Scott says, “but we really need to do better at maintaining the weight loss once it happens. »
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