ATLAS study: How weight loss benefits the health of fat tissue

A study led by Assistant Professor Anne Loft, Associate Professor Jesper Grud Skat Madsen and Professor Susanne Mandrup from University of Southern Denmark sheds light on what happens in the fat tissue during weight loss. All three are leading researchers at the Center of Excellence ATLAS, which investigates the molecular mechanisms driving changes in liver and fat tissues in response to obesity and weight loss. This knowledge is important because obesity-induced dysfunction in these two tissues drive the development of metabolic diseases, such as diabetes and cardiovascular diseases.

Changes in adipose tissue during weight loss in the ATLAS study: The study followed individuals with severe obesity before and after weight loss, achieved through lifestyle interventions and bariatric surgery. By analyzing subcutaneous adipose tissue samples using single-cell sequencing, the researchers mapped changes in adipose tissue cell populations and their gene activity during weight loss. Created in BioRender. Loft, A. (2026) https://BioRender.com/cmo7azo. Credit: Anne Loft/SDU

Using advanced single-cell analyses, the researchers have now carefully analysed the cellular and molecular changes in fat tissue from patients with severe obesity at three key stages:

• When patients were first scheduled for gastric bypass surgery.

• After a moderate weight loss of 5–10% through dietary changes, just before surgery.

• Two years post-surgery, after substantial weight loss of 20–45%.

"When we analysed the adipose tissue samples taken two years after 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,” explained Loft. "This is one of the most important improvements after weight loss because 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. So, when inflammation and immune cells decrease, it's a clear benefit for health."

The researchers also observed a significant increase in blood vessel cells, which likely helps deliver oxygen and nutrients more efficiently to fat tissue - another positive adaptation. Moreover, gene expression in all cell types was normalised to the lean state.

But what about the moderate weight loss phase? Clinically, it's known that even a 5% drop in weight improves whole-body insulin sensitivity. So, the team examined the corresponding fat tissue.

"At this stage, we didn't see a drop in inflammation," added Loft, "meaning that the improvement in insulin sensitivity is unlikely to be driven by reduced inflammation in fat tissue."

According to Mandrup, it has long been known that modest weight loss yields health benefits, but it has been unclear whether the health of the fat tissue itself is also improved.

"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 explained. "This suggests that modest weight loss may promote formation of new and healthier fat cells, which may contribute to the improved insulin sensitivity. Our study indicates that even modest weight loss in these patients can benefit the health of the fat tissue. 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."

The findings were featured in the paper, 'Single-cell-resolved transcriptional dynamics of human subcutaneous adipose tissue during lifestyle- and bariatric surgery-induced weight loss', published in Nature Metabolism. To access this paper, please click here (log-in maybe required)