TY - JOUR
T1 - Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning
AU - Bayindir, Irem
AU - Babaeikelishomi, Rohollah
AU - Kocanova, Silvia
AU - Sousa, Isabel Sofia
AU - Lerch, Sarah
AU - Hardt, Olaf
AU - Wild, Stefan
AU - Bosio, Andreas
AU - Bystricky, Kerstin
AU - Herzig, Stephan
AU - Vegiopoulos, Alexandros
N1 - Publisher Copyright:
© Copyright © 2015 Bayindir, Babaeikelishomi, Kocanova, Sousa, Lerch, Hardt, Wild, Bosio, Bystricky, Herzig and Vegiopoulos.
PY - 2015/8/17
Y1 - 2015/8/17
N2 - De novo formation of beige/brite adipocytes from progenitor cells contributes to the thermogenic adaptation of adipose tissue and holds great potential for the therapeutic remodeling of fat as a treatment for obesity. Despite the recent identification of several factors regulating browning of white fat, there is a lack of physiological cell models for the mechanistic investigation of progenitor-mediated beige/brite differentiation. We have previously revealed prostacyclin (PGI2) as one of the few known endogenous extracellular mediators promoting de novo beige/brite formation by relaying β-adrenergic stimulation to the progenitor level. Here, we present a cell model based on murine primary progenitor cells defined by markers previously shown to be relevant for in vivo browning, including a simplified isolation procedure. We demonstrate the specific and broad induction of thermogenic gene expression by PGI2 signaling in the absence of lineage conversion, and reveal the previously unidentified nuclear relocalization of the Ucp1 gene locus in association with transcriptional activation. By profiling the time course of the progenitor response, we show that PGI2 signaling promoted progenitor cell activation through cell cycle and adhesion pathways prior to metabolic maturation toward an oxidative cell phenotype. Our results highlight the importance of core progenitor activation pathways for the recruitment of thermogenic cells and provide a resource for further mechanistic investigation.
AB - De novo formation of beige/brite adipocytes from progenitor cells contributes to the thermogenic adaptation of adipose tissue and holds great potential for the therapeutic remodeling of fat as a treatment for obesity. Despite the recent identification of several factors regulating browning of white fat, there is a lack of physiological cell models for the mechanistic investigation of progenitor-mediated beige/brite differentiation. We have previously revealed prostacyclin (PGI2) as one of the few known endogenous extracellular mediators promoting de novo beige/brite formation by relaying β-adrenergic stimulation to the progenitor level. Here, we present a cell model based on murine primary progenitor cells defined by markers previously shown to be relevant for in vivo browning, including a simplified isolation procedure. We demonstrate the specific and broad induction of thermogenic gene expression by PGI2 signaling in the absence of lineage conversion, and reveal the previously unidentified nuclear relocalization of the Ucp1 gene locus in association with transcriptional activation. By profiling the time course of the progenitor response, we show that PGI2 signaling promoted progenitor cell activation through cell cycle and adhesion pathways prior to metabolic maturation toward an oxidative cell phenotype. Our results highlight the importance of core progenitor activation pathways for the recruitment of thermogenic cells and provide a resource for further mechanistic investigation.
KW - PGI
KW - adipocyte cell model
KW - adipocyte progenitors
KW - adipose tissue remodeling
KW - beige/brite differentiation
KW - nuclear localization
KW - prostacyclin
UR - http://www.scopus.com/inward/record.url?scp=84956709773&partnerID=8YFLogxK
U2 - 10.3389/fendo.2015.00129
DO - 10.3389/fendo.2015.00129
M3 - Article
AN - SCOPUS:84956709773
SN - 1664-2392
VL - 6
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
M1 - 129
ER -