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Mature Human White Adipocytes Cultured under Membranes Maintain Identity, Function, and Can Transdifferentiate into Brown-like Adipocytes

Research output: Contribution to journalArticle

Matthew J. Harms, Qian Li, Sunjae Lee, Cheng Zhang, Bengt Kull, Stefan Hallen, Anders Thorell, Ida Alexandersson, Carolina E. Hagberg, Xiao-Rong Peng, Adil Mardinoglu, Kirsty L. Spalding, Jeremie Boucher

Original languageEnglish
Pages (from-to)213-225
JournalCell Reports
Volume27
Issue number1
DOIs
Publication statusPublished - 2 Apr 2019

King's Authors

Abstract

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.

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