Adipose tissue is a dynamic organ influencing metabolism and inflammation. It is well known that obesity leads to major remodeling of the adipose tissue, including low-grade inflammation and dysfunction of the tissue. But it is not clear whether the tissue can revert to a lean state in response to different modes of weight loss?
Researchers from the Loft, Madsen, and Mandrup groups at ATLAS set out to explore this question in detail using advanced single-cell sequencing technologies. Their findings, now published in Nature Metabolism, uncover a fascinating adaptation process.
When the researchers analyzed adipose tissue after substantial surgery-induced weight loss, the changes were striking.
“We saw that there was a drastic reduction in immune cells, especially the so-called lipid-associated macrophages (LAMs), actually down to levels seen in lean individuals," says co-first author and bioinformatician Rasmus Rydbirk. The team also observed increased vascularization of the tissue, further indicating that adipose tissue has the capacity to return to a lean-like state after substantial weight loss.
Such improvements were not seen after modest weight loss.
“Inflammation and vascularization remained largely unchanged at this stage,” explains Anne Loft. “However, interestingly, we found an expansion of a specific population of adipose stem cells and activation of gene programs related to adipocyte differentiation. This regeneration process appears to be an early response to weight loss, helping the tissue to become healthier.”
The study highlights adipose tissue’s remarkable plasticity.
“Even small reductions in weight has the ability to start a cascade of cellular changes in adipose tissue,” concludes Susanne Mandrup. “Understanding the molecular mechanisms of these processes is key to tackling obesity-related complications.”
For a more detailed news piece on the ATLAS study, please navigate to the Faculty of Science's latest news
The work is supported by grants from Danish National Research Foundation, the Novo Nordisk Foundation and the Lundbeck Foundation