Microphysiological system recapitulating the pathophysiology of adipose tissue in obesity

Abstract

A growing body of evidence has indicated that white adipose tissue (AT) remodeling is a major trigger for obesity-associated metabolic complications. However, the scarcity of translational models is an obstacle to the development of medicines that act on adipose restoration. Here, we describe a microphysiological system (MPS) that emulates the unique features of reprogrammed AT as a new in vitro tool for studying AT pathophysiology in obesity. The AT MPS contained mature adipocytes embedded in an extracellular matrix (ECM) hydrogel interfaced with AT microvascular endothelium, which was constantly perfused with fresh media. The unique biochemical signals due to the remodeled ECM in obesity were recapitulated using a decellularized AT ECM (AT dECM) hydrogel, which preserves the features of altered ECM composition in obesity. The mature adipocytes embedded in the AT dECM hydrogel maintained their function and morphology for a week without dedifferentiation. Using the AT MPS, we successfully modeled inflammation-induced AT microvascular dysfunction, the recruitment of immune cells due to the upregulation of cell adhesion molecules, and higher cancer cell adhesion as an indicator of metastasis, which are observed in obese individuals. The AT MPS may therefore represent a promising platform for understanding the dynamic cellular interplay in obesity-induced AT remodeling and validating the efficacy of drugs targeting AT in obesity.