High salt supplementation of a MASH-inducing diet causes lean MASH phenotype with increased hepatic urea cycle activity and EIF5A hypusination

Western diet + fructose (WDF) causes obesity and MASH. Surprisingly, high salt supplementation of WDF (HSWDF) produced a lean MASH phenotype with significant inflammation and fibrosis, and reduced steatosis.

Interestingly, we observed decreased urea cycle activity leading to reduced eukaryotic translation initiation factor 5A hypusination (Eif5aH) and impaired mitochondrial protein synthesis in mice fed WDF. High saltsupplementation unexpectedly improved these changes to improve hepatic fatty acid oxidation and steatosis. Additionally, single-cell sequencing revealed that high salt induced pro-inflammatory responses in hepatic immune cell subpopulations.