White adipose tissue plays a central role in energy homeostasis by storing excess energy within the lipid droplet of white adipocytes, but it also exerts metabolic and endocrine functions, notably secreting hormones such as resistin and leptin. In mice, it is distributed across several depots of distinct developmental origins: subcutaneous inguinal, perigonadal, mesenteric, and perirenal. In contrast, brown adipose tissue dissipates energy as heat thanks to its numerous mitochondria and the constitutive activation of the uncoupling protein Ucp1. A third cell type, the beige adipocyte, arises within white tissue and shares the thermogenic markers of brown adipocytes. In mice, this "browning" is induced by prolonged cold exposure, fasting, or exercise, and is of metabolic interest as it promotes fat combustion.
The transcription factor Egr1 has been described as a regulator of white and beige differentiation programs. Egr1 overexpression has been associated with obesity in both humans and mice, whereas animals lacking Egr1 display increased energy expenditure and protection against high-fat diet-induced obesity. The authors had previously shown that these mice spontaneously develop browning of the subcutaneous inguinal white adipose tissue, in the absence of any external stimulation.
The present study delves further into this phenomenon by combining the analysis of adipose depots from eight-month-old female mice with cellular models. Adipose-derived stem/stromal cells (mASC) from Egr1+/+ and Egr1-/- mice, as well as C3H mesenchymal stem cells expressing or not expressing Egr1, were subjected to white and beige differentiation protocols and then characterized by Oil Red O staining and gene expression quantification using quantitative PCR. The work demonstrates that Egr1-mutant mice display an increase in Ucp1 expression specifically restricted to the subcutaneous tissue, with no equivalent change in the other depots. This feature is accompanied by a shift toward an oxidative, brown-type metabolism. At the cellular level, Egr1 proves to be necessary and sufficient to promote the differentiation of white adipocytes and to impair that of beige adipocytes.
These results confirm the role of Egr1 in directing adipocyte differentiation programs and highlight the depot-specific nature of its action. According to the authors, modulating Egr1 expression could constitute a promising therapeutic strategy to increase energy expenditure and limit the metabolic disorders associated with obesity.