Fig. 1. The inhibitor LPT1 blocks ferroptosis without disrupting iron accumulation in a mouse MAFLD model.

a Schematic representation of experimental design illustrating the treatment protocol with liproxstatin-1 (LPT1) in a high-fat high-fructose diet (HFHF)-induced MAFLD mouse model. C57BL/6 J mice were divided into four groups: Chow, Chow+LPT1, HFHF and HFHF + LPT1 groups. MAFLD was induced by HFHF diet for 16 weeks. LPT1 was given intraperitoneally (10 mg·kg⁻¹·d⁻¹) for two weeks. b Effect of LPT1 treatment on body weight and liver weight. c, d Fe²⁺ levels and GSH levels in liver tissues of four groups of mice. e, f Representative immunoblot and quantitative analysis of GPX4 protein level in liver tissues of four groups of mice. GAPDH as loading control. n = 4 biologically independent experiments. g–i Representative immunoblot and quantitative analysis of ACSL4 and ALOX15 protein levels in liver tissues of four groups of mice. GAPDH as loading control. n = 4 biologically independent experiments. j The mRNA level of Hamp in liver tissues of four groups of mice. n = 6 biologically independent experiments. k Immunoblotting analysis of 4-hydroxynonenal (4-HNE)-adducted protein levels in liver tissues of four groups of mice. n = 6 biologically independent experiments. l Malondialdehyde (MDA) levels in liver tissues of four groups of mice. n  = 6 biologically independent experiments. The data were presented as Means ± SEM and analyzed by One way-ANOVA followed by Tukey’s post hoc test. *P < 0.05, **P < 0.01 vs Chow; ^#P < 0.05, ^##P < 0.01 vs HFHF. NS no significance.