Abstract
In mice, exercise, cold exposure and fasting lead to the differentiation of inducible-brown adipocytes, called beige adipocytes, within white adipose tissue and have beneficial effects on fat burning and metabolism, through heat production. This browning process is associated with an increased expression of the key thermogenic mitochondrial uncoupling protein 1, Ucp1. Egr1 transcription factor has been described as a regulator of white and beige differentiation programs, and Egr1 depletion is associated with a spontaneous increase of subcutaneous white adipose tissue browning, in absence of external stimulation. Here, we demonstrate that Egr1 mutant mice exhibit a restrained Ucp1 expression specifically increased in subcutaneous fat, resulting in a metabolic shift to a more brown-like, oxidative metabolism, which was not observed in other fat depots. In addition, Egr1 is necessary and sufficient to promote white and alter beige adipocyte differentiation of mouse stem cells. These results suggest that modulation of Egr1 expression could represent a promising therapeutic strategy to increase energy expenditure and to restrain obesity-associated metabolic disorders.
Highlights
In mice, exercise, cold exposure and fasting lead to the differentiation of inducible-brown adipocytes, called beige adipocytes, within white adipose tissue and have beneficial effects on fat burning and metabolism, through heat production
We previously demonstrated that mice lacking Egr[1] expression exhibit spontaneous browning of the inguinal subcutaneous white adipose tissue without external stimulation[20]
These observations are consistent with previous results showing the absence of spontaneous browning in brown adipose tissue (BAT) and GAT from Egr1-deleted mice[23]
Summary
Exercise, cold exposure and fasting lead to the differentiation of inducible-brown adipocytes, called beige adipocytes, within white adipose tissue and have beneficial effects on fat burning and metabolism, through heat production. To further characterize the role of Egr[1] in SC-WAT browning, adipose stem cells (mASC) were isolated from control Egr1+/+ and mutant Egr1−/− SC-WAT and compared for their ability to differentiate into white or beige adipocytes in vitro. These results indicate that Egr[1] loss-of-function increases Cebpb, Ucp[1] and Dcun1d3 expression and decreases Lep expression in SC-WAT, resulting in spontaneous browning in this specific adipose tissue depot.
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