Fig. 7: Pharmacological inhibition of SREBP1 rescues the exacerbated MASLD phenotype in TIA1-deficient mice. | Cell Death & Disease

Fig. 7: Pharmacological inhibition of SREBP1 rescues the exacerbated MASLD phenotype in TIA1-deficient mice.

From: Hepatocyte TIA1 constrains metabolic steatohepatitis by translationally suppressing Srebf1 mRNA in stress granules

Fig. 7: Pharmacological inhibition of SREBP1 rescues the exacerbated MASLD phenotype in TIA1-deficient mice.

A–G TIA1-Flox and TIA1-HKO mice with the SREBP1 inhibitor PF-429242 (20 mg/kg/d) or vehicle control for the final 8 weeks of a 12-week HFD regimen (n = 10 mice per group). A Average daily food intake measured over 3 consecutive days (Left panel) and liver to body weight ratios (%) (Right panel) in the indicated groups. (n = 10 per group; mean ± SEM). B Representative gross morphological photographs of livers from the indicated experimental groups, showing that PF-429242 treatment ameliorates the hepatomegaly and pale appearance in HKO-HFD mice. C Representative photomicrographs of liver sections stained with H&E, ORO, F4/80, and αSMA. Scale bar: 100 μm. D Biochemical analyses of hepatic TC and TG levels, and serum AST and ALT activities (n = 10 per group; mean ± SEM). E Western blot analysis of key proteins involved in fatty acid metabolism (FASN, mature SREBP1, SCD1, and PPARγ) in liver lysates from the indicated groups. GAPDH served as a loading control. F Densitometric quantification of western blotting results shown in (E). (n = 3 biologically independent mice per condition; mean ± SEM). G Hepatic mRNA expression levels of genes related to lipid metabolism (Fasn, Srebf1, Scd1 and Pparg), and inflammation (Il1β, Il6 and Tnfα), normalized to Gapdh. (n = 5 biologically independent mice per condition; mean ± SEM). *P < 0.05, **P < 0.01, ***P < 0.001; ****P < 0.0001; ns indicates not significant.

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