Fig. 1: Downregulation of A1AT under MASLD/MASH conditions exacerbates hepatic inflammation and fibrosis.

a‒d, Two replicative secretome proteomics analyses of CM from NCD- and FFD-fed (24-week-old) mice indicating total clustered proteins (a), secreted proteins (b), significantly different proteins (c) and differentially secreted proteins (d). e, Enrichment analysis of downregulated proteins revealed in the secretome proteomics study. f, The list of proteins from the secretome proteomics analysis showing the relative fold change compared with NCD–HCM. g, Relative hepatic tissue expression of Serpina1c-e mRNA in the NCD- and FFD-fed mice. h, Serum levels of A1AT detected in the NCD- and FFD-fed mice via ELISA. i, Correlations of A1AT, PR3 and the PR3/A1AT ratio with the serum ALT level in the NCD- and FFD-fed mice. j, Protein expression of A1AT in the hepatic tissue of preclinical models, such as the FFD (24 week feeding), HFD (24 week feeding), MCD (4 week feeding) and MCD–HFD (6 week feeding)-induced MASLD models. k, Human gene expression of A1AT in accordance with different disease states, fat composition, BMI, inflammation score and NAS. l, Detection of the serum levels of A1AT and PR3 and the PR3/A1AT ratio in the control group (healthy) and patients with MASLD via ELISA. m, Detection of A1AT protein expression in control groups (healthy) and patients with MASH via IHC staining. n, Correlations of A1AT, PR3 and the PR3/A1AT ratio with the serum ALT and AST levels in the control group (healthy) and patients with MASLD. The data are presented as the means ± s.d., n ≥ 5; *^,#P < 0.05, **^,##P < 0.01, ^***,###P < 0.001 and ^****,####P < 0.0001 versus the control model. ns, not significant.