Cells in the body remember obesity. Here’s what that means for weight loss

# Cells in the Body Remember Obesity: Here’s What That Means for Weight Loss Obesity leaves a lasting imprint on fat and immune cells in ways that might make weight regain harder to avoid. Weight loss is notoriously hard to maintain. Within a few years, most people regain the pounds they initially lose, whether through dieting, exercise, surgery, or weight-loss medications such as the popular glucagon-like peptide 1 (GLP-1) drugs. Recent research suggests fat cells’ “memory” could explain why. Cells that store fat, or adipocytes, and immune cells, such as macrophages, in fat tissue can remember weight long after it’s lost. Scientists suggest obesity causes lasting changes to those cells that make it easier for the body to revert to a state of obesity, even after significant weight loss. The changes are etched into the cells’ epigenome, which instructs each cell on how to read specific genes that control their function, as explained by Ferdinand von Meyenn, who studies nutrition and metabolic epigenetics at the Swiss Federal Institute of Technology Zurich. This ensures that a liver cell doesn’t suddenly behave like a neuron, for example. In individuals with obesity, lasting epigenetic changes might prime the body to regain weight more easily if they consume more calories. Von Meyenn’s team used RNA sequencing to compare gene activity in individual cells from fat tissue of those with obesity before they had bariatric surgery to similar tissue from individuals without obesity. Even after participants with obesity lost about 25 percent of their body mass index post-surgery, some of their genes remained out of alignment. This suggests some fat tissue didn’t fully recover from obesity; certain genes controlling metabolic function and inflammation remained abnormally switched on or off. Previous studies showed that fat cells in obese mice also retain epigenetic alterations, even after the animals slim down. When they were later fed a high-fat diet, these mice regained weight faster than control animals. Lab tests indicated that fat cells from the obese mice absorbed glucose and lipids more readily. Von Meyenn noted that while fat cells normally take in sugars and lipids, these obesity-altered cells appeared “slightly tweaked” to absorb more of those nutrients. Additional research demonstrated that immune cells might also remember prior weight. When a person gains weight, different types of immune cells infiltrate expanding fat tissue, likely as a stress response, according to William Scott, an obesity researcher at Imperial College London. His research showed that after bariatric surgery, the number of immune cells in individuals’ fat tissue decreased dramatically, but not everything reset completely. The immune cells retained inflammatory characteristics developed during periods of obesity. Findings from mouse studies indicated that weight cycling—losing and regaining weight—can intensify these immune cell changes and worsen metabolic health more than never losing the weight. The duration of this epigenetic memory is unclear, but fat cells can persist for up to a decade in humans, giving those cells the potential to maintain long-term changes, as noted by von Meyenn. It’s believed that changes may also be happening in the brain, liver, and muscle, which von Meyenn plans to investigate next. These findings don’t imply that weight loss is futile; even short-term weight loss correlates with improvements in metabolic health. However, the research may help explain why weight relapse is so common and why avoiding weight gain matters. In an environment and society that foster prevalent weight gain, prevention becomes much easier said than done. Researchers, including von Meyenn, are currently exploring 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 varying effects on these cells. “There’s a big drive to make our weight-loss drugs, like GLP-1 medications, more potent to cause greater weight reductions,” Scott mentioned, “but we really need to do better at maintaining weight loss once it’s happening.”