As a possible mechanism underlying protective effects of GDF15 on NASH-related fibrosis, we found that treatment with pharmacological doses of GDF15 directly suppressed expression of fibrosis-related genes and OPN in HSCs in vitro, although the expression of these genes in HSCs treated with physiological/pathological doses (0.3–1 ng/ml) of GDF15 was not changed. This evidence concerns the gene SPP1 and metabolic dysfunction-associated steatohepatitis.