Extended Data Fig. 8: AAV8-shGpnmb alleviates established MASH without affecting systemic metabolism.
(a to q) Eight-week-old male WT mice were fed the AMLN diet for 4 months to induce MASH. At this point, a subset was euthanized (4 months). The remaining mice were injected with AAV8-shNC or -shGpnmb and fed the AMLN diet for 2 additional months (a). BW (b), food intake (c), hepatic GPNMB (d), serum G-ECD (e), H&E and Oil Red O staining, α-SMA immunostaining, and Sirius Red staining, scale bar, 200 μm; representative gross appearance of livers, scale bar, 5000 μm (f), histological evaluation (g), liver TG (h), serum AST and ALT (i) (4 months n = 8; shNC n = 7; shGpnmb n = 7 mice). Hepatic gene expression (n = 7 mice per group) (j and k). Fat mass/BW and lean mass/BW ratios (l), weights of eWAT, ingWAT, and BAT, and their BW ratios (m), serum TG and TC (n), and blood glucose (o) (4 months n = 8; shNC n = 7; shGpnmb n = 7 mice). GTT and ITT (shNC n = 5; shGpnmb n = 4 mice) (p), and energy expenditure (n = 6 mice per group) (q). Data are presented as mean ± SEM (b, e, g-q). Unpaired two-tailed Student’s t-test (b, j-l, p, q) and one-way ANOVA followed by Tukey’s multiple-comparison test (e, g-i, m-o).
