Mature Human White Adipocytes Cultured under Membranes Maintain Identity, Function, and Can Transdifferentiate into Brown-like Adipocytes.
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Harms MJ, Li Q, Lee S, Zhang C, Kull B, Hallen S, Thorell A, Alexandersson I, Hagberg CE, Peng XR, Mardinoglu A, Spalding KL, Boucher J
Cell Reports 27 (1) 213-225.e5 [2019-04-02; online 2019-04-04]
White adipose tissue (WAT) is a central factor in the development of type 2 diabetes, but there is a paucity of translational models to study mature adipocytes. We describe a method for the culture of mature white adipocytes under a permeable membrane. Compared to existing culture methods, MAAC (membrane mature adipocyte aggregate cultures) better maintain adipogenic gene expression, do not dedifferentiate, display reduced hypoxia, and remain functional after long-term culture. Subcutaneous and visceral adipocytes cultured as MAAC retain depot-specific gene expression, and adipocytes from both lean and obese patients can be cultured. Importantly, we show that rosiglitazone treatment or PGC1α overexpression in mature white adipocytes induces a brown fat transcriptional program, providing direct evidence that human adipocytes can transdifferentiate into brown-like adipocytes. Together, these data show that MAAC are a versatile tool for studying phenotypic changes of mature adipocytes and provide an improved translational model for drug development.
PubMed 30943403
DOI 10.1016/j.celrep.2019.03.026
Crossref 10.1016/j.celrep.2019.03.026
pii: S2211-1247(19)30342-0