Probing Insulin Sensitivity with Metabolically Competent Human Stem Cell-Derived White Adipose Tissue Microphysiological Systems.

ABSTRACT: Impaired white adipose tissue (WAT) function has been recognized as a critical early event in obesity-driven disorders, but high buoyancy, fragility, and heterogeneity of primary adipocytes have largely prevented their use in drug discovery efforts highlighting the need for human stem cell-based approaches. Here, human stem cells are utilized to derive metabolically functional 3D adipose tissue (iADIPO) in a microphysiological system (MPS). Surprisingly, previously reported WAT differentiation approaches create insulin resistant WAT ill-suited for type-2 diabetes mellitus drug discovery. Using three independent insulin sensitivity assays, i.e., glucose and fatty acid uptake and suppression of lipolysis, as the functional readouts new differentiation conditions yielding hormonally responsiv

SUBMITTER: Qi L 

PROVIDER: S-EPMC8776615 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature