The FGL1-LAG-3 axis attenuates melanoma-induced cachexia in mice.

Cachexia is a debilitating condition characterized by the wasting of adipose and skeletal muscle tissues, resulting in significant weight loss and frailty. It is responsible for 20% of cancer-related mortalities. Despite its clinical significance, the precise mechanisms underlying cachexia remain inadequately understood. Our gene expression analysis of white adipose tissues has identified an upregulation of fibrinogen-like protein 1 (FGL1) in B16F10 tumor-bearing mice. In this study, we demonstrate that the intraperitoneal administration of FGL1 protein mitigates tumor-induced wasting of adipose and muscle tissues in mice. Correspondingly, FGL1 treatment reverses the expression patterns of genes associated with lipid metabolism and muscle degradation. Mechanistically, our research establishes that lymphocyte activation gene-3 (LAG-3) serves as a critical mediator of FGL1’s anti-cachexia effects. These findings suggest that FGL1 acts as a crucial intermediary between tumor presence and the processes of adipose catabolism and muscle wasting, thereby identifying the FGL1-LAG-3 signaling axis as a promising therapeutic target for cancer cachexia.