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Sci Rep. 2017 Nov 23;7(1):16153. doi: 10.1038/s41598-017-16543-7.

Egr1 deficiency induces browning of inguinal subcutaneous white adipose tissue in mice.

Author information

1
Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR7622, Inserm U1156, IBPS-Developmental Biology Laboratory, F-75005, Paris, France.
2
University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
3
École normale supérieure, PSL Research University, CNRS, Inserm, Institut de Biologie de l'École normale supérieure (IBENS), Plateforme Génomique, 75005, Paris, France.
4
Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR7622, Inserm U1156, IBPS-Developmental Biology Laboratory, F-75005, Paris, France. delphine.duprez@upmc.fr.
5
Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR7622, Inserm U1156, IBPS-Developmental Biology Laboratory, F-75005, Paris, France. emmanuelle.havis@upmc.fr.

Abstract

Beige adipocyte differentiation within white adipose tissue, referred to as browning, is seen as a possible mechanism for increasing energy expenditure. The molecular regulation underlying the thermogenic browning process has not been entirely elucidated. Here, we identify the zinc finger transcription factor EGR1 as a negative regulator of the beige fat program. Loss of Egr1 in mice promotes browning in the absence of external stimulation and leads to an increase of Ucp1 expression, which encodes the key thermogenic mitochondrial uncoupling protein-1. Moreover, EGR1 is recruited to the proximal region of the Ucp1 promoter in subcutaneous inguinal white adipose tissue. Transcriptomic analysis of subcutaneous inguinal white adipose tissue in the absence of Egr1 identifies the molecular signature of white adipocyte browning downstream of Egr1 deletion and highlights a concomitant increase of beige differentiation marker and a decrease in extracellular matrix gene expression. Conversely, Egr1 overexpression in mesenchymal stem cells decreases beige adipocyte differentiation, while increasing extracellular matrix production. These results reveal a role for Egr1 in blocking energy expenditure via direct Ucp1 transcription repression and highlight Egr1 as a therapeutic target for counteracting obesity.

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