(The) roles of GATA3 in white adipose tissue browning

Abstract

Adipose tissue plays a key role in the regulation of homeostasis via dissipation and accumulation of energy and it is associated with a metabolic disorder. Brown fats specialize in energy consumption by activating heat production. Surprisingly white fats also have the function of thermogenic activation. It is called “browning’, which has the same function of thermogenesis as brown fat. Based on this, GATA3 was discovered by screening for browning regulatory factors. We investigated that GATA3 can enhance the thermogenesis by regulating the expression of thermogenic genes such as UCP-1. Overexpression of GATA3 increases the expression of UCP-1 and other thermogenic genes with norepinephrine. The ablation of GATA3 retracts the expression of UCP-1 and thermogenic genes. Of note, the luciferase activity in UCP-1 promoter is dose-dependently increased by GATA3. We confirmed that GATA3 interacts with the coactivator PGC-1$\alpha$ to increase the expression of UCP-1. The interaction of GATA3 and PGC-1$\alpha$ is essential for increasing the expression of UCP-1. Finally, we confirmed the GATA3 has the function of enhanced energy expenditure by increasing thermogenic genes in-vivo. Thus, GATA3 could be used as a valuable target for regulating thermogenic capacity and consequently to overcome obesity.