A physiological adipose-on-chip disease model to mimic adipocyte hypertrophy and inflammation in obesity

Abstract

The adipose tissue is a metabolically active endocrine organ with a dynamic secretome that is known to be implicated in metabolic disorders. Various studies have demonstrated detrimental downstream endocrinal effects of dysfunctional adipose tissue on other metabolic tissues, such as skeletal muscle and liver. In vitro ‘Adipose-on-Chip’ (AOC) models have been developed as an animal-alternative experimental platform to mimic adipose dysfunction in metabolic diseases. However, existing AOCs have not modeled both overtime lipid accumulation and inflammation of adipocytes in the presence of excess circulating free fatty acids (FFA), which are hallmarks of dysfunctional adipose tissue in obesity. This study reports for the first time, the establishment of a physiologically-relevant AOC disease model, which mimics adipose tissue pathophysiology in obesity via excessive FFA loading. The AOC model supports 3D perfusion culture of human bone marrow mesenchymal stem cell (BMMSC) differentiated adipocytes with improved adipogenic phenotypes as compared to conventional 2D well-plate cultures. Adipocytes in the AOC can be induced into a diseased phenotype on-chip, where they become both hypertrophic and inflamed when treated with an FFA mixture. This AOC disease model provides a more physiological experimental system to study the effects of adipose tissue dysfunction on downstream tissues for mechanistic investigations into obesity-related metabolic diseases.