DDIT3 and metabolic dysfunction-associated steatohepatitis: However, others have demonstrated metformin to increase hepatic GDF15 mRNA and secretion via activating transcription factor 4 (AFT4) and CCAAT-enhancer-binding protein homologous protein (CHOP) involved in cell stress (13, 31), a signaling pathway also found in a mouse model of non-alcoholic steatohepatitis to increase the GDF15 mRNA level in the liver (36).