Stromalab - Targeting the stroma to regenerate Médecine régénératrice, thérapie cellulaire, cellules souches mésenchymateuses, tissu adipeux, moelle osseuse, réparation, régénération Regenerative medicine, cell therapy, mesenchymal stem cells, adipose tissue, bone marrow, repair, regeneration

Diabetes may be promoted by precursors of travelling adipocytes

The presence of fat cells outside the fat tissue disrupts metabolism and promotes the development of complications such as type 2 diabetes. By describing the underlying mechanism, based on the release of adipocyte precursors from subcutaneous tissue, researchers identified a biomarker potential for individual diabetes risk.

 

The presence of fat cells (or adipocytes) in tissues other than fat tissue is abnormal. It is even known to be harmful to metabolism, with an increased risk of developing type 2 diabetes in overweight or obese people. Until now, it has been accepted that these “ectopic” adipocytes were derived from local precursors. But researchers at StromaLab* in Toulouse have just described that this abnormal presence is set up at a distance, from adipocyte precursors – adipocyte stromal cells (ASCs) – released by subcutaneous adipose tissue and able to migrate, for example, into skeletal muscle tissue.

The researchers explored the phenomenon in mice. They showed that a high-fat diet, maintained for 8 weeks, leads to the release and migration of CFS to skeletal muscle. They become adult and functional, and promote the development of type 2 diabetes. In a second step, the researchers were able to obtain the same metabolic disorders without enriching the animals’ diet, by administering a molecule known to facilitate the “detachment” of CSAs from subcutaneous adipose tissue. This molecule, AMD3100, stimulates the chemokine-receptor pair CXCL12/CXCR4. “These two results put side by side clearly illustrate that metabolic deregulation is linked to mobilized cells and not to another biological pathway mediated, for example, by dietary lipids themselves,” explains Coralie Sengenès who led this work.

 

Prevent and predict

Ultimately, understanding how ectopic fat tissue is formed could help monitor the individual risk of metabolic complications: “For the same overweight person, a person with predominantly subcutaneous fat tissue has a much lower risk of metabolic complications than a person with predominantly visceral fat tissue. Now that we have described that metabolic disorders are linked to the migration of cells from subcutaneous adipose tissue, we want to develop a prognostic tool. We will work with physicists specialized in microfluidics to develop methods for collecting and characterizing circulating cells in the blood. If this work is successful, it will be possible to assess a patient’s risk of type 2 diabetes based on the determination of their circulating CSA level.

At the same time, researchers are devising ways to block the CSA release mechanism, for example by targeting the CXCL12/CXCR4 couple. Such a strategy opens up new perspectives in the prevention or treatment of obesity complications: “We have observed that the use of an anti-diabetic drug, pioglitazone, reduces the development of diabetes in mice. The drug works by normalizing the functioning of fat cells, but especially by preventing them from being released from subcutaneous tissue by inhibiting the CXCR4” receptor. This approach will of course have to be studied in more depth, in animals and then in humans, before new treatments can be developed.