Fig. 1: Downregulation of S100A10 and S100A11 reduces MASH development induced by a Fructose Palmitate Cholesterol-enriched diet.

A Experimental design of the fructose/palmitate/cholesterol-enriched diet (FPC) protocol, including feeding period and AAV8 injections. B Liver triglyceride content measured by colorimetric method following Folch’s extraction of total lipids. C57BL/6J mice were injected with AAV8-shCTL (n = 10), AAV8-shS100A10 (n = 10), or AAV8-shS100A11 (n = 12) and fed during 10 weeks with FPC. C Automatic detection of lipid droplets numbers in the livers of C57BL/6J mice injected with AAV8-shCTL (n = 11), AAV8-shS100A10 (n = 11), or AAV8-shS100A11 (n = 12) and fed for 10 weeks with FPC. Results are normalized to total tissue area. D Automatic detection of individual lipid droplets size in the livers of C57BL/6J mice injected with AAV8-shCTL (n = 11), AAV8-shS100A10 (n = 11), or AAV8-shS100A11 (n = 12) and fed for 10 weeks with FPC. Results are expressed as the average lipid droplet size per mouse. E Representative images of Masson’s Trichrome coloration in the liver of C57BL/6J mice injected with AAV8-shCTL, AAV8-shS100A10, or AAV8-shS100A11 and fed for 24 weeks with FPC. Scale bar: 200 µm. F Automatic detection of collagen deposition extent based on Masson’s coloration in the liver of C57BL/6J mice injected with AAV8-shCTL (n = 9), AAV8-shS100A10 (n = 9), or AAV8-shS100A11 (n = 10) and fed for 24 weeks with FPC. Results are expressed as the percentage of Masson’s Trichrome positive area on the total area of the tissue. G Quantification of macrophages density measured by Iba1 immunohistochemistry in the liver of C57BL/6J mice injected with AAV8-shCTL (n = 9), AAV8-shS100A10 (n = 11), or AAV8-shS100A11 (n = 9) and fed during 10 weeks with FPC. Results are expressed as the percentage of Iba1+ area over the total tissue area. H Liver TNFα content measured by ELISA in C57BL/6J mice injected with AAV8-shCTL (n = 6), AAV8-shS100A10 (n = 6), or AAV8-shS100A11 (n = 7) and fed for 10 weeks with FPC. Results are presented as means +/− S.E.M. “n” represents the number of animals. * = p < 0.05; ** = p < 0.01; **** = p < 0.0001 determined by One-Way ANOVA followed by Dunnett’s post-hoc analysis.