%0 Journal Article
%T Integrative clinical and preclinical studies identify FerroTerminator1 as a potent therapeutic drug for MASH.
%A Tao L
%A Yang X
%A Ge C
%A Zhang P
%A He W
%A Xu X
%A Li X
%A Chen W
%A Yu Y
%A Zhang H
%A Chen SD
%A Pan XY
%A Su Y
%A Xu C
%A Yu Y
%A Zheng MH
%A Min J
%A Wang F
%J Cell Metab
%V 0
%N 0
%D 2024 Aug 12
%M 39142286
%F 31.373
%R 10.1016/j.cmet.2024.07.013
%X The complex etiological factors associated with metabolic dysfunction-associated fatty liver disease (MAFLD), including perturbed iron homeostasis, and the unclear nature by which they contribute to disease progression have resulted in a limited number of effective therapeutic interventions. Here, we report that patients with metabolic dysfunction-associated steatohepatitis (MASH), a pathological subtype of MAFLD, exhibit excess hepatic iron and that it has a strong positive correlation with disease progression. FerroTerminator1 (FOT1) effectively reverses liver injury across multiple MASH models without notable toxic side effects compared with clinically approved iron chelators. Mechanistically, our multi-omics analyses reveal that FOT1 concurrently inhibits hepatic iron accumulation and c-Myc-Acsl4-triggered ferroptosis in various MASH models. Furthermore, MAFLD cohort studies suggest that serum ferritin levels might serve as a predictive biomarker for FOT1-based therapy in MASH. These findings provide compelling evidence to support FOT1 as a promising novel therapeutic option for all stages of MAFLD and for future clinical trials.