bims-hypusi 2026-07-12 papers

Issue of 2026–07–12
two papers selected by
Sebastian J. Hofer, Max Delbrück Center

Mol Metab. 2026 Jul 08. pii: S2212-8778(26)00101-8. [Epub ahead of print] 102417

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

Shaopeiwen Luo, Norihiko Morisawa, Anissa Anindya Widjaja, Brijesh Kumar Singh, Derek John Hausenloy, Paul Michael Yen, Jin Zhou.

MASLD/MASH can occur in lean individuals; however, the environmental triggers and molecular mechanisms underlying lean MASH are unclear, and suitable animal models are lacking. Mice fed a Western diet with liquid fructose (WDF) develops obesity and MASH (obese MASH). In contrast, high salt supplementation of WDF (HSWDF) produced a lean MASH phenotype with reduced steatosis but induced significant inflammation and fibrosis (lean MASH). In WDF-induced obese MASH, we observed decreased urea cycle activity and flux, along with reduced eukaryotic translation initiation factor 5A hypusination (EIF5AH) and mitochondrial biosynthesis. High salt supplementation of WDF unexpectedly ameliorated these alterations, enhanced hepatic fatty acid oxidation and reduced hepatosteatosis. However, single-cell sequencing revealed that dietary high salt was associated with pro-inflammatory responses in hepatic immune cell subpopulations. In summary, we have established a dietary mouse model of lean MASH that differs from obese-MASH in hepatic urea cycle, mitochondrial protein synthesis, and immune cell activation, providing new mechanistic insight into lean MASH.

Keywords: EIF5A hypusination; Excess Dietary salt; Obese MASH; Urea Cycle; lean-MASH

DOI: https://doi.org/10.1016/j.molmet.2026.102417

NPJ Biofilms Microbiomes. 2026 Jul 07.

Gut-derived cinnamic acid limits allergic airway inflammation via the SAT1-spermidine-eIF5A hypusination axis.

Yujia He, Jing Liu, Zhihan Yang, Xiao Zhang, Yuanming Huang, Liqiong Song, Zhihong Ren.

The gut-lung axis is a critical regulator of systemic immune homeostasis, however, the precise mechanisms linking gut-derived metabolites to distal airway inflammation remain incompletely understood. Here, we show that oral administration of viable Leuconostoc mesenteroides MY2024 engages a metabolite-host enzyme circuit that protects against allergic airway inflammation (AAI). Viable, but not heat-inactivated, MY2024 significantly attenuated ovalbumin (OVA)-induced Th2-driven eosinophilic asthma by suppressing pathogenic M2-like macrophage responses in the lung. Mechanistically, MY2024 increased gut-derived cinnamic acid (CA), which activated a colonic STAT1-SAT1 signaling axis to accelerate systemic spermidine catabolism. Reduced systemic spermidine availability was associated with reduced pulmonary eIF5A hypusination, a metabolic checkpoint known to support alternative macrophage activation. Notably, these protective effects and the associated metabolic reprogramming were preserved in microbiota-depleted mice, highlighting a direct bacterium-to-host metabolic axis. Together, our findings delineate a probiotic-metabolite-host enzyme circuit and identify colonic epithelial SAT1-dependent spermidine catabolism as a potential metabolic checkpoint for regulating type 2 AAI.

DOI: https://doi.org/10.1038/s41522-026-01089-2