Nrg4 Secreted by Brown Adipose Tissue Suppresses Ferroptosis of Sepsis-Induced Liver Injury.

Abstract

Sepsis is a leading cause of death, with the liver being particularly vulnerable to sepsis-related injuries. This damage significantly contributes to disease progression, underscoring the need for new treatments. Brown adipose tissue (BAT) secretes various cytokines, including neuregulin 4 (Nrg4), which plays a protective role in hepatic glucose and lipid metabolism. Ferroptosis, a key type of cell death in sepsis-induced liver injury, has recently gained attention. This study aimed to investigate how BAT-secreted cytokines alleviate liver ferroptosis in sepsis. Septic liver injury was induced in the control and BAT group using cecal ligation and puncture (CLP) and lipopolysaccharide injections. BAT removal worsened ferroptosis; in contrast, CL316243 activation reduced it. These findings suggest that Nrg4 secretion following BAT activation protects the liver during sepsis by inhibiting ferroptosis. Future therapies targeting BAT activation and Nrg4 could potentially mitigate sepsis-induced liver damage, offering new insights into treatment strategies.