Fat-On-A-Chip Models for Research and Discovery in Obesity and Its Metabolic Comorbidities

Abstract

The obesity epidemic and its associated comorbidities 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 bioactive adipokines such as adiponectin and leptin, as well as systemic metabolic dysfunction. The majority of current obesity research has focused primarily on preclinical animal models in vivo and two-dimensional cell culture models in vitro. Neither of these generalized approaches is optimal due to interspecies 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 to reproduce 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 3D 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, nonalcoholic fatty liver disease, and osteoarthritis.

Breast Cancer Reconstruction: Design Criteria for a Humanized Microphysiological System

“…32 Comparable MPS models have been created using human adipose-derived cells as recently reviewed. 74 In one format, fragments of intact human adipose tissue are sandwiched between sheets of adherent ASC. These remained viable as 3D constructs for up to 8 weeks in vitro while retaining physiological function based on adipokine secretion and signaling response.…”

Harnessing the power of microphysiological systems for COVID-19 research

“… [3] , [4] , [5] These systems include organ-on-a-chip, organoid, and bioreactor models, with multiple human cell types under physical forces, such as fluid flow, interacting to create complex structures and reproduce biological activities, such as barrier function, [6] membrane transport, [7] neuronal network signaling, [8] , [9] thrombosis, [10] and metabolism. [11] , [12] …”

Modeling Adipogenesis: Current and Future Perspective

“…Recently, on-a-chip technology is emerging in many research fields, aiming to mimic pathological and physiological microenvironment at organ level. In the field of adipogenesis, fat-on-a-chip models have been developed [ 121 , 122 , 123 ]. The models can be integrated with multiplexed immunoassay and imaging technology, allowing high-content analysis of single-cell data.…”