A new study conducted in Denmark has revealed how moderate weight loss can increase the health of fat, or body adipose tissue, even though cells retain an epigenetic ‘memory’ of their obese state. The research team analyzed cellular and molecular changes in adipose tissue in severely obese patients before and after gastric bypass surgery.

Obesity typically causes inflammation and dysfunction of adipose tissue, increasing the risk of developing metabolic diseases such as type 2 diabetes and cardiovascular disease.

Although weight loss may reduce the risk of developing these diseases, the researchers note that this is one of the first studies to show that weight loss can rebuild healthy fat tissue.

“When we analyzed adipose tissue samples taken two years later, we found that [gastric bypass] After the surgery, I lost a lot of weight and the changes were noticeable. “The number of immune cells was significantly reduced, and some types of immune cells were reduced to levels normally seen in lean people,” said study leader Anne Loft, assistant professor at the University of Southern Denmark.

She emphasized that this is one of the most important improvements after weight loss, noting that immune cells contribute to inflammation in adipose tissue and reduced insulin sensitivity.

“This local insulin resistance can have systemic effects, increasing the risk of type 2 diabetes and other obesity-related diseases over time,” she explains. “Therefore, reducing inflammation and immune cells has clear health benefits.”

After significant weight loss, adipose tissue becomes similar to that of a lean person.Loft’s team also found that weight loss caused a significant increase in blood vessel cells, suggesting that this likely helps deliver oxygen and nutrients to fat tissue more efficiently.

Additionally, they note that gene expression in all cell types was normalized in the lean state.

“Our study shows that even modest weight loss in these patients can benefit adipose tissue health,” Loft says. “After significant weight loss, adipose tissue closely resembles that of lean people, suggesting that the ‘memory’ of obesity is not as durable as previously thought.”

This “memory” that causes obesity was first documented in a study published in 2024. natureThe researchers hypothesized that this is a significant cause for people struggling to maintain weight loss, and argued that this contributes to the problematic “yo-yo” effect commonly seen in diets.

Generation of healthier fat cells

Co-author Suzanne Mandrup said scientists have long known that moderate weight loss has health benefits. However, in a recently published study, natural metabolism This suggests that this may include the production of healthier fat cells.

“Using single-cell technology, we found that certain types of preadipocytes were increased, increasing gene activity that promotes the production of new fat cells,” Mandrup explains. “This suggests that moderate weight loss may promote the formation of new, healthier fat cells and contribute to improved insulin sensitivity.”

The research team set out to pinpoint how obesity and weight loss trigger the molecular mechanisms that cause changes in the liver and adipose tissue. This involved identifying what cellular and molecular adaptations are occurring in the adipose tissue of severely obese patients.

The team monitored three key stages. When the patient was first scheduled for gastric bypass surgery. Immediately before surgery and after moderate weight loss of 5-10% due to dietary changes. Two years after surgery after significant weight loss of 20-45%.

Clinically, even a 5% decrease in body weight improved whole-body insulin sensitivity. However, during the moderate weight loss phase before surgery, the researchers were unable to see a reduction in inflammation, Loft says.

“This means that improved insulin sensitivity is unlikely to be caused by reduced inflammation in adipose tissue.”

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