Scientists discover weight loss can regenerate healthy fat tissue

New research from Denmark reveals how moderate weight loss can boost the health of adipose or body fat tissue, despite cells retaining an epigenetic “memory” of the obese state. The team analyzed cellular and molecular changes in fat tissue from patients with severe obesity before and after gastric bypass surgery.

Obesity typically leads to fat tissue inflammation and dysfunction, which increases the risk of developing metabolic diseases, such as type 2 diabetes and cardiovascular diseases.

Although weight loss may lower the risk of developing these diseases, the researchers note this is one of the first studies that indicates that healthy fat tissue can be reestablished by weight loss.

“When we analyzed the adipose tissue samples taken two years after [gastric bypass] surgery, following considerable weight loss, the changes were striking. The number of immune cells was greatly reduced — and several types of immune cells were down to levels normally seen in lean individuals,” says study lead Anne Loft, an assistant professor at the University of Southern Denmark.

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

“This local insulin resistance can affect the whole body and, over time, increase the risk of type 2 diabetes and other obesity-related diseases,” she explains. “So when inflammation and immune cells decrease, it’s a clear benefit for health.”

After major weight loss, the fat tissue largely resembles that of lean individuals.Loft’s team also noticed weight loss caused a significant increase in blood vessel cells, which they suggest will likely help deliver oxygen and nutrients more efficiently to fat tissue.

Moreover, they note that gene expression in all cell types was normalized in a lean body state.

”Our study indicates that even modest weight loss in these patients can benefit the health of the fat tissue,” says Loft. “After major weight loss, the fat tissue largely resembles that of lean individuals, suggesting that the ‘memory’ of obesity is not as persistent as previously thought.”

This obesogenic “memory” was first recorded in a 2024 study published in Nature, where researchers posited it as a significant cause among people struggling to maintain weight loss — contributing to the problematic “yo-yo” effect often seen with dieting.

Genesis of healthier fat cells

According to co-author Susanne Mandrup, scientists have long known that modest weight loss supports health benefits. However, the latest study published in Nature Metabolism suggests this may include the genesis of healthier fat cells.

“Using single-cell technologies, we saw an increase in a specific type of pre-fat cell and a boost in gene activity promoting the creation of new fat cells,” Mandrup explains. “This suggests that modest weight loss may promote the formation of new and healthier fat cells, which may contribute to the improved insulin sensitivity.”

The team set out to pinpoint how obesity and weight loss trigger molecular mechanisms that cause changes in the liver and fat tissues. This involved identifying what cellular and molecular adaptations were taking place in fat tissue from patients with severe obesity.

The team monitored three key stages: when patients were first scheduled for gastric bypass surgery; just before surgery, soon after a moderate weight loss of 5–10% through dietary changes; and two years post-surgery, following substantial weight loss of 20–45%.

Clinically, even a 5% drop in weight improved whole-body insulin sensitivity. However, at the moderate weight-loss phase before surgery, the researchers didn’t see a drop in inflammation, says Loft. 

“This means that the improvements in insulin sensitivity are unlikely to be driven by reduced inflammation in fat tissue.”

Earlier this week, medical and wellness portal WebMD launched its adjacent website, Embody, which offers expert-reviewed nutrition guidance and workshops for weight loss. The new platform features a multidisciplinary approach, combining cognitive behavioral therapy with expert-led workshops on sleep, nutrition, and exercise.