Microphysiological Modeling of Vascular Adipose Tissue for Multi-Throughput Applications

Abstract

Adipose tissue (AT) is a highly vascularized endocrine organ which regulates whole-body metabolic homeostasis. Key AT functions which rely on vascularization include insulin-stimulated glucose uptake and lipolysis (lipid mobilization to supply energy). Most in vitro AT models do not include the vasculature, and while microphysiological systems (MPS) incorporate spatial organization of cells, 3D environments, and perfusion by external pumps, they are too large to fit traditional cultureware. Thus, we developed a novel miniaturized vascularized adipose tissue ({micro}AT) platform compatible with traditional 24 well plates. Using this {micro}AT platform, we quantified vascular permeability and adipocyte function by insulin-stimulated glucose uptake and lipolysis assays. Shear flow decreased vascular permeability and increased insulin-stimulated glucose uptake. Treatment with forskolin, an adenyl cyclase agonist, increased lipolysis, and decreased vascular permeability. This {micro}AT platform allows for the facile screening of compounds in a physiologically relevant system where both adipocyte and vascular function can be evaluated.