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Innovative model system to study obesity

obesity and type 2 diabetes mellitus

Obesity rarely comes alone. Pathological obesity is often accompanied by diseases such as diabetes. Especially the white adipose tie plays a central role in the development of the metabolic disease. Researchers at the NMI Natural and Medical Sciences Institute in Reutlingen have now developed an innovative mix& in cooperation with the Medical Faculty of the University of Tubingen and the Fraunhofer Institute IGB Match organ-on-chip model. Research published in the journal Advanced Science shows how the chip can be used to simulate a wide variety of aspects of obesity disease on an individual basis – without any animal testing at all.

From the first second until about 25. The first year of life – during this period a person gains weight, develops and grows until they reach their final body weight. Our body always knows when our hunger has been satisfied and all the necessary substances have been absorbed. As a result, a feeling of satiety occurs. If this signal is missing or ignored, the way is paved for obesity to develop. However, it is not uncommon for malnutrition to be behind morbid obesity.

In principle, abnormal weight gain is a risk factor for a variety of diseases. In addition to type 2 diabetes mellitus, cardiovascular and neurological diseases, obesity promotes at least 13 different types of cancer. The consequences of obesity can be serious and are therefore not only a current but also a very important area of research.

A look into the fatty tie

Adipose tie can be divided into different types, white, brown/beige and pink adipose tie. In addition to color, tie types differ in their unique cell composition and function. If we take a closer look at the components of white adipose tie, we can find the specialists of fat metabolism, the white fat cells. They take care of fat deposits – i.e. the energy reserves -. Influence energy metabolism through hormone release. Furthermore, a large number of immune cells can be found in the white adipose tie. When overeating occurs, fat cells multiply, grow in size and trigger a cascade of inflammatory processes.

Adipose tie in research

For some time, science has been concerned with causes and treatment options for obesity, but an optimal experimental platform with a valid predictive power has not yet been developed. Health risks for patients make direct research on humans impossible. Accordingly, many scientists relied on animal experiments to better understand the pathophysiological mechanisms behind the disease. However, the low transferability of results from animals to humans severely limits the validity of animal experiments. It remains to look into the petri dish. What possibilities do cell cultures offer?

The research group led by Prof. Dr. Peter Loskill, group leader at the NMI and bridge professor at the Medical Faculty of the University of Tubingen, who headed the Attract group Organ-on-a-Chip at Fraunhofer IGB from 2016 to 2021, is developing customized organ-on-chip technologies. These special chips integrate living substructures of organs into a controlled microenvironment. The chips consist of small three-dimensional chambers and channels on a micrometer scale and map the functionality or disease of an organ. First systems of the working group could only cultivate fat cells. The new innovative mix& Match System also integrates all the major cellular components also found in human white adipose tie.

"The next-generation obesity chip is characterized by its high flexibility and modularity. In addition to energy storage and mobilization, the chip can also be used to simulate adipose tie-specific hormone release and include a wide range of inflammatory processes. This multidimensional approach is unique!", emphasizes Prof. Loskill.

In the future, the novel system will offer scientists a humane alternative to animal testing. As a result, not only could lipid metabolism research and drug development benefit from the new test platform, but personalized medicine could also be advanced.

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