Cell子刊：揭开FGF21为何能够逆转严重脂肪肝

Core Viewpoint - Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are increasingly serious public health burdens with limited treatment options. Recent studies indicate that fibroblast growth factor-21 (FGF21) analogs can significantly improve MASH, although the mechanisms remain unclear [2]. Group 1 - A study published by researchers from the University of Iowa in Cell Metabolism demonstrates that FGF21 reverses MASH through coordinated actions on the central nervous system (CNS) and liver [3]. - The research team established that FGF21 exerts beneficial metabolic effects to reverse MASH by independently reducing liver triglyceride and cholesterol levels through different mechanisms [5]. - FGF21 signaling directly acts on glutamatergic neurons in the CNS, stimulating the reduction of liver triglycerides and reversing fibrosis, while also directly signaling liver cells to lower cholesterol levels [6][8]. Group 2 - Mechanistically, FGF21 increases sympathetic nervous activity in the liver, thereby inhibiting de novo lipogenesis [7]. - The core findings of the study include that FGF21 can reverse diet-induced MASH, directly signals the CNS to lower liver triglyceride levels and fibrosis, signals liver cells to reduce cholesterol during MASH, and enhances liver sympathetic nervous activity while decreasing de novo lipogenesis [8]. - Overall, these findings provide a promising drug target and new insights for the treatment of MASH [10].