# The Proteomic Profiling of Circulating Extracellular Vesicles of Western Diet and Chemical‐Induced Murine MASH Model

## TL;DR

This study identifies proteomic signatures in extracellular vesicles that could serve as non-invasive biomarkers for tracking liver disease progression in mice.

## Contribution

The study introduces novel proteomic biomarkers for differentiating MASLD and MASH stages using circulating extracellular vesicles.

## Key findings

- Ctsb and Psap are associated with early MASLD, while F13a1 and Pigr are linked to early MASH.
- Psma2, Psmb3, and Psmb5 are enriched in severe MASH stages.
- EV-associated proteins show potential as non-invasive biomarkers for liver disease monitoring.

## Abstract

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is an increasingly prevalent chronic liver condition that can progress to severe complications such as metabolic dysfunction‐associated steatohepatitis (MASH). Despite its growing burden, there are no reliable non‐invasive biomarkers for tracking disease progression. In this study, we established a murine MASLD/MASH model using a high‐fat diet and chemical (CCl4) induction. We analyzed serum‐derived extracellular vesicles (EVs) at 14 and 28 weeks to identify stage‐specific proteomic signatures. Proteomic profiling of circulating EVs revealed key proteins associated with disease progression, including cathepsin B (Ctsb) and prosaposin (Psap) in early MASLD, and coagulation factor XIII A chain (F13a1) and polymeric immunoglobulin receptor (Pigr) in early MASH. The significant and severe MASH stages notably enriched Psma2, Psmb3, and Psmb5. These findings suggest EV‐associated proteins may be promising non‐invasive biomarkers for differentiating MASLD/MASH stages and guiding clinical monitoring.