PT - JOURNAL ARTICLE AU - Cécile Milet AU - Marianne Bléher AU - Kassandra Allbright AU - Mickael Orgeur AU - Fanny Coulpier AU - Delphine Duprez AU - Emmanuelle Havis TI - Egr1 deficiency induces browning of inguinal subcutaneous white adipose tissue in mice AID - 10.1101/150003 DP - 2017 Jan 01 TA - bioRxiv PG - 150003 4099 - http://biorxiv.org/content/early/2017/06/14/150003.short 4100 - http://biorxiv.org/content/early/2017/06/14/150003.full AB - 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 activates Ucp1 that 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 decrease in extracellular matrix gene expression. Conversely, Egr1 overexpression in mesenchymal stem cells decreases beige adipocyte differentiation, while increasing extracellular matrix production. These results uncover the role of Egr1 in blocking energy expenditure via direct Ucp1 transcription regulation and highlight Egr1 as a therapeutic target for counteracting obesity.