Cell https://doi.org/10.1016/j.cell.2019.07.033 (2019)

GDF15, a member of the TGF-β family of cytokines, signals through its receptor GFRAL, expressed on neurons in the brain stem, to mediate appetite-suppressive effects. In Cell, Medzhitov and colleagues show that GDF15 coordinates tolerance to inflammatory damage through the regulation of triglyceride metabolism. GDF15 is upregulated in the serum of patients with sepsis and in the myeloid and non-hematopoietic cells of mice challenged with lipopolysaccharide or the synthetic RNA duplex poly(I:C). During bacterial or viral infection, neutralization of GDF15 increases mortality and cardiac and renal injury, with no effect on the amount of pro-inflammatory cytokines or the pathogen burden. GDF15 blockade reduces the production of triglyceride species in the liver in a manner dependent on β-adrenergic signaling. Administration of triglycerides rescues GDF15-neutralized mice from the mortality and cardiac damage, while subcutaneous administration of GDF15 improves survival in sterile and infectious models of sepsis.