Fat-on-a-Chip models for research and discovery in obesity and its metabolic co-morbidities.

The obesity epidemic and its associated co-morbidities present a looming challenge to health care delivery throughout the world. Obesity is characterized as a sterile inflammatory process within adipose tissues leading to dysregulated secretion of bio-active adipokines such as adiponectin and leptin as well as systemic metabolic dysfunction. The majority of current obesity research has focused primarily on pre-clinical animal models in vivo and two-dimensional (2D) cell culture models in vitro. Neither of these generalized approaches is optimal due to inter-species variability, insufficient accuracy with respect to predicting human outcomes, and failure to recapitulate the three-dimensional (3D) microenvironment. Consequently, there is a growing demand and need for more sophisticated microphysiological systems (MPS) in order to re-produce more physiologically accurate human white and brown/beige adipose depots. To address this research need, human and murine cell lines and primary cultures are being combined with bioscaffolds to create functional 3-dimensional environments that are suitable for metabolically active adipose organoids in both static and perfusion bioreactor cultures. The development of these technologies will have considerable impact on the future pace of discovery for novel small molecules and biologics designed to prevent and treat metabolic syndrome and obesity in humans. Furthermore, when these adipose tissue models are integrated with other organ systems they will have applicability to obesity-related disorders such as diabetes, non-alcoholic fatty liver disease, and osteoarthritis.