Human adipose tissue organoids developed to treat obesity

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 (Image: Pixabay CC0)
(Image: Pixabay CC0)

Long thought to be non-existent in humans, brown and beige adipose tissue plays a key role in our body’s energy homeostasis. Nevertheless, they are in short supply in our bodies, and observing them in situ is not easy. A French scientific team1 from Inserm, ESF and Toulouse III - Paul Sabatier University, led by Professor Louis Casteilla and based at the Restore Institute (CNRS/EFS/Inserm/UT3), has developed a unique process to generate them in the laboratory in the form of organoids. Their study was published in Advanced Science on September 21.

Fat may not get much press, but it’s essential to the proper functioning of our bodies. Since 2009 and the discovery of new types of adipose tissue in humans, both brown and beige, biological research in this field has accelerated. White adipose tissue accounts for over 95% of body fat. It helps regulate energy metabolism by storing and releasing the energy we need to live.

Brown adipose tissue has an entirely different role: it participates in adaptive thermogenesis. In other words, it dissipates stored energy in the form of heat, thereby regulating body temperature. However, it has been found to be dysfunctional in obese patients, as well as during aging. It therefore appears to be an object of study and a major therapeutic target.

Given its low quantity in the body, stimulating the conversion of white adipose tissue into beige tissue, whose properties are very similar to those of brown tissue, is the avenue favoured by scientists. Until now, in vitro study models have been limited to conventional two-dimensional cell cultures in Petri dishes, far from reproducing the complex three-dimensional context of tissue in vivo. On the other hand, animal-based models do not present the same physiology of these tissues as humans.

The multidisciplinary collaboration of the teams involved in the scientific study has enabled the development of a unique tissue engineering process for generating pre-vascularized organoids of human beige adipose tissue of variable dimensions. Organoids are increasingly used in medical research to produce models capable of mimicking the physiology of human tissues by reproducing their structural complexity and cellular variety. They can be used both for the development of in vitro tests as an alternative to animal experimentation, and for their transplantation for therapeutic purposes.

By creating an appropriate biochemical and biomechanical microenvironment using hydrogel and defined growth-inducing factors, the scientists have developed a unique engineering process required for the emergence of millimeter-sized adipose tissue organoids, as well as centimeter-sized micro-tissues. Two patents have been filed for this work.

1 Collaboration between the Restore Institute (CNRS/EFS/Inserm/UT3), the Systems Analysis and Architecture Laboratory (LAAS-CNRS) and the Valrose Biology Institute (iBV, CNRS/Inserm/Université côte d’azur).