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

TY - JOUR

T1 - Mature Human White Adipocytes Cultured under Membranes Maintain Identity, Function, and Can Transdifferentiate into Brown-like Adipocytes

AU - Harms, Matthew J.

AU - Li, Qian

AU - Lee, Sunjae

AU - Zhang, Cheng

AU - Kull, Bengt

AU - Hallen, Stefan

AU - Thorell, Anders

AU - Alexandersson, Ida

AU - Hagberg, Carolina E.

AU - Peng, Xiao-Rong

AU - Mardinoglu, Adil

AU - Spalding, Kirsty L.

AU - Boucher, Jeremie

PY - 2019/4/2

Y1 - 2019/4/2

N2 - 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.

AB - 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.

KW - adipocyte

KW - white adipose

KW - WAT

KW - brown adipose

KW - BAT

KW - transdifferentiation

KW - UCP1

KW - culture

KW - MAAC

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85063422988&origin=SingleRecordEmailAlert&dgcid=raven_sc_search_en_us_email&txGid=a03f9b01426e0cf28b40f11b241dce9e

U2 - 10.1016/j.celrep.2019.03.026

DO - 10.1016/j.celrep.2019.03.026

M3 - Article

SN - 2211-1247

VL - 27

SP - 213

EP - 225

JO - Cell Reports

JF - Cell Reports

IS - 1

ER -