Fig. 1: Viscoelasticity is increased in the livers of individuals with NASH and T2DM and in mice on a HiAD.
From: Matrix viscoelasticity promotes liver cancer progression in the pre-cirrhotic liver
a, Schematic of AGE increase in NASH/T2DM. b–f. b, Quantification of AGEs in the liver. c, Schematic of the AFM analysis. Indent-retract was used to generate force–distance curves. d–f, The stiffness (d; Young’s modulus), representative force–distance curves (e) and quantification of hysteresis area (f, viscoelasticity) were assessed using AFM. The average stiffness of the human cirrhotic liver is indicated by a dashed line. n = 4 (healthy controls), n = 6 (patients with NASH), n = 4 (T2DM) and n = 5 (NASH + T2DM) individuals. g–k, Rheometry analysis of fresh liver tissues. g, Schematic of rheometry analysis of fresh liver tissues. h, Rheometry analysis of the storage modulus in precirrhotic livers. i, The loss tangent (viscoelasticity) in the livers of healthy participants, and individuals with NASH, T2DM or NASH/T2DM. j, Stress relaxation curves in liver samples from the different patient groups. Norm., normalized. k, Stress was normalized to the initial stress and depicted as τ1/2 (the timescale at which the stress is relaxed to half its original value). n = 4 (healthy controls), n = 4 (patients with NASH), n = 4 (T2DM) and n = 6 (NASH + T2DM) individuals. l–p, Mice were placed onto a chow or FFD diet, or a HiAD diet with daily vehicle, AGE inhibitor (PM) or AGE-cross-linking inhibitor (alagebrium, ALT-711) treatment. l, Schematic of the experiment. i.p., intraperitoneal. m, Quantification of liver AGEs (from left to right, n = 8, 7, 9, 5 and 5). n–p, Liver stiffness (n; from left to right, n = 5, 5, 8, 9 and 6 mice) and viscoelasticity (stress relaxation curves (o) and hysteresis area (p); n = 5 mice in each group) were assessed using AFM. q–t, Stiffness (q) and viscoelasticity (r–t) were assessed using rheometry. From left to right, n = 5, 5, 8, 9 and 6 (q and r) and n = 7, 7, 8, 9 and 6 (t) mice. The diagrams in a and l were created using BioRender. Data are mean ± s.e.m. n values refer to individual mice. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by Tukey’s multiple-comparison test (b–q and t) and two-sided Student’s unpaired t-tests (b, f and r). NS, not significant; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
