Growth differentiation factor 15: Emerging role in liver diseases

Growth differentiation factor 15 (GDF15) is a cell stress-response cytokine within the transforming growth factor-β (TGFβ) superfamily. It is known to exert diverse effects on many metabolic pathways through its receptor GFRAL, which is expressed in the hindbrain, and transduces signals through the downstream receptor tyrosine kinase Ret. Since the liver is the core organ of metabolism, summarizing the functions of GDF15 is highly important. In this review, we assessed the relevant literature regarding the main metabolic, inflammatory, fibrogenic, tumorigenic and other effects of GDF15 on different liver diseases, including Metabolic dysfunction-associated steatotic liver disease(MASLD), alcohol and drug-induced liver injury, as well as autoimmune and viral hepatitis, with a particular focus on the pathogenesis of MASLD progression from hepatic steatosis to MASH, liver fibrosis and even hepatocellular carcinoma (HCC). Finally, we discuss the prospects of the clinical application potential of GDF15 along with its research and development progress. With better knowledge of GDF15, increasing in-depth research will lead to a new era in the field of liver diseases.