White adipose tissue (WAT) makes up about one fifth of a healthy adult’s body mass. Besides being the main storage depot for excess dietary energy, WAT is also recognized as the largest endocrine gland in the human body regulating metabolic events like appetite or satiety. Consequently, abnormal WAT function is a risk factor for metabolic disorders such as obesity or type 2 diabetes. Moreover, it is of utmost importance when it comes to drug testing since it is capable of manipulating the mode of action and consequentially the efficacy of drugs. Yet, despite its significance, WAT is frequently underestimated, and there is still plenty of research to be done on the underlying mechanisms associating WAT to human pathophysiology. We therefore developed a human microphysiological system (MPS) featuring 3D vascularized adipose tissue. The potential applications of our developed WAT-on-a-Chip systems are eminently multifarious and expand from individual or multi-organ-integration drug testing platforms to possibilities of disease modelling and personalized medicine.
Diseases originate from the disruption of pathways, usually involving more than one organ. Insulin resistance is an example of multi-organ dysfunction and is one of the key factors for non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome development and progression. Both diseases have an immense societal and economic impact. The biological mechanisms triggering the onset of the diseases are still poorly understood in part, due to the lack of human relevant disease models that consider more than one tissue. The study of the crosstalk between liver and adipose tissue including its immune component is essential for the understanding of insulin resistance triggering events.
The activation of brown and beige adipose tissue (BAT) and “browning”, (generation of BAT in white fat tissue depots) has aroused great interest in biomedical research in the last few years. This is mainly due to the decoupling of the mitochondrial respiratory chain in BAT, a biochemical process that is showing considerable potential for new therapeutic approaches, in particular to obesity and diabetes. However, studies with human tissue are still rare and difficult to carry out at present. Concepts and technologies to examine browning for pharmacological studies and personalized medicine currently exist only to a limited extent.
We have developed an innovative microfluidic system for the integration of (beige) adipose tissue. This BAT-on-a-chip makes a variety of different assays possible, e. g. to examine activation / blocking of the functionality of BAT, the induction of browning in white adipose tissue, and characterization of endocrine and metabolic function of BAT. The BAT-on-the chip system opens up diverse possibilities as an in-vitro model for general screens to identify substances that induce browning, as well as for approaches to examine patient-specific effects of therapy approaches.
Funding: DAAD PPP; Marie Skłodowska-Curie Actions (MSCA);
J. Rogal, J. Roosz, C. Teufel, M. Cipriano, R. Xu, W. Eisler, M. Weiss, K. Schenke-Layland, P. Loskill
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WAT-on-a-chip integrating human mature white adipocytes for mechanistic research and pharmaceutical applications
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P. Loskill, T. Sezhian, K.M. Tharp, F.T. Lee-Montiel, S. Jeeawoody, W.M. Reese, P.-J.H. Zushin, A. Stahl, K.E. Healy
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