Fig. 3: Conditional hepatic deletion of G3BP1 exacerbates HFHC-induced MASH. | Nature Communications

Fig. 3: Conditional hepatic deletion of G3BP1 exacerbates HFHC-induced MASH.

From: Dysregulation of GTPase-activating protein-binding protein1 in the pathogenesis of metabolic dysfunction-associated steatotic liver disease

Fig. 3

A Gross hepatic morphology and liver weight quantification (right panels) of WT and G3BP1 LKO mice fed NC or high-fat high-cholesterol diet (HFHC) for 24 weeks (n = 6 mice per group). All values are presented as means ± S.E.M. *P < 0.05; ****P < 0.0001, analysis of two-way ANOVA followed by Sidak’s post hoc test for multiple comparisons (two-sided). B The liver/body weight ratio of G3BP1 LKO and WT mice after NC or HFHC consumption for 24 weeks (n = 6 mice per group). All values are presented as means ± S.E.M. ****P < 0.0001, ***P < 0.001, analysis of two-way ANOVA followed by Sidak’s post hoc test for multiple comparisons (two-sided). C Representative H&E-stained liver sections from WT and G3BP1 LKO mice fed NC or HFHC for 24 weeks (n = 6), imaged by Leica microscope (scale bars: 50 µm). D Sirius red-stained liver sections from WT and G3BP1 LKO mice fed NC or HFHC for 24 weeks (n = 6), imaged by Leica microscope (scale bars: 50 µm). E Intraperitoneal glucose tolerance tests (GTT) in WT and G3BP1 LKO mice fed NC or HFHC for 24 weeks (n = 6 mice per group), with blood glucose monitored at 0/15/30/60/90/120 min and area under curve (AUC) calculated by trapezoidal method. All values are presented as means ± S.E.M. Statistical analysis was performed using two-way ANOVA followed by Sidak’s post hoc test for multiple comparisons (two-sided). Exact p values are shown in the figure. *: WT-NC vs. WT-HFHC; #: LKO-HFHC vs. WT-HFHC. F Intraperitoneal insulin tolerance tests (ITT) in WT and G3BP1 LKO mice fed NC or HFHC for 24 weeks (n = 6 mice per group), with blood glucose monitored at 0/15/30/60/90 min and area under curve (AUC) calculated by trapezoidal method; All values are presented as means ± S.E.M. Statistical analysis was performed using two-way ANOVA followed by Sidak’s post hoc test for multiple comparisons (two-sided). Exact p values are shown in the figure. *: WT-NC vs. WT-HFHC; #: LKO-HFHC vs. WT-HFHC. ALT (G) and AST (H) concentrations measured in WT and G3BP1 LKO mice fed NC or HFHC for 24 weeks (n = 6 mice per group), All values are presented as means ± S.E.M. ****P < 0.0001, analysis of two-way ANOVA followed by Sidak’s post hoc test for multiple comparisons (two-sided). The liver TC (I) and TG (J) levels of the G3BP1 LKO and WT mice fed normal control diet or HFHC (n = 6 mice per group). All values are presented as means ± S.E.M. ****P < 0.0001, analysis of two-way ANOVA followed by Sidak’s post hoc test for multiple comparisons (two-sided). K–P Quantitative RT-PCR analysis of fibrogenesis-related genes (Acta2, Col1a1, Tgfb1, Timp1) and inflammatory markers (Tnf-α, Il6) in liver tissues from WT and G3BP1 LKO mice with MASH induced by 24-week HFHC diet (n = 6 mice per group). Gene expression was normalized to Gapdh and is presented as mean ± S.E.M. Statistical significance was assessed using unpaired two-tailed Student’s t-test. Exact p values are as follows: (K)Acta2, ***P = 0.0008; (L)Col1a1, **P = 0.0015; (M)Tgfb1, ****P < 0.0001; (N) Timp1, ***P = 0.0007; (O) Tnf-α, ***P = 0.0010; (P)Il6, ***P = 0.0003.

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