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Probing Insulin Sensitivity with Metabolically Competent Human Stem Cell-Derived White Adipose Tissue Microphysiological Systems.
Qi, Lin; Zushin, Peter-James H; Chang, Ching-Fang; Lee, Yue Tung; Alba, Diana L; Koliwad, Suneil K; Stahl, Andreas.
Afiliação
  • Qi L; Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, CA, 94720, USA.
  • Zushin PH; Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, CA, 94720, USA.
  • Chang CF; Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, CA, 94720, USA.
  • Lee YT; Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, CA, 94720, USA.
  • Alba DL; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, 94143, USA.
  • Koliwad SK; Diabetes Center, University of California, San Francisco, San Francisco, CA, 94143, USA.
  • Stahl A; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, 94143, USA.
Small ; 18(3): e2103157, 2022 01.
Article em En | MEDLINE | ID: mdl-34761526
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 responsive iADIPO are derived. Through concomitant optimization of an iADIPO-MPS, it is abled to obtain WAT with more unilocular and significantly larger (≈40%) lipid droplets compared to iADIPO in 2D culture, increased insulin responsiveness of glucose uptake (≈2-3 fold), fatty acid uptake (≈3-6 fold), and ≈40% suppressing of stimulated lipolysis giving a dynamic range that is competent to current in vivo and ex vivo models, allowing to identify both insulin sensitizers and desensitizers.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resistência à Insulina Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resistência à Insulina Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article