Circulating exosomal microRNAs offer a non-invasive biomarker for MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a global public health challenge with rapidly rising prevalence, especially in China. Despite advances in treatment, the underlying molecular mechanisms remain incompletely understood. A new research article published in the Chinese Medical Journal on March 16, 2026, provides critical insights into the role of exosomal microRNAs (miRNAs) in MASLD pathogenesis.

The research team, led by experts from Shandong First Medical University, China, collected plasma samples from six patients with MASLD and six healthy volunteers. They isolated and characterized exosomes, then performed miRNA expression profiling. Results showed that exosomal miR-122-3p and miR-3614-5p were significantly elevated in patients with MASLD compared with controls.

In vitro experiments using oleic acid-treated HepG2 and Bel-7404 cells demonstrated that only miR-122-3p induced triglyceride accumulation and reactive oxygen species production, hallmarks of MASLD. Engineered exosomes overexpressing miR-122-3p replicated these pathological effects and suppressed adenosine 5'-monophosphate-activated protein kinase (AMPK) activity, a key energy-sensing pathway protective against liver steatosis.

Mechanistically, luciferase reporter assays confirmed fibroblast growth factor receptor 4 (FGFR4) as a direct target of miR-122-3p. Overexpression of miR-122-3p reduced FGFR4 protein levels, while FGFR4 overexpression reversed the metabolic damage caused by miR-122-3p, including lipid deposition, oxidative stress, and AMPK inactivation. The study validates the miR-122-3p/FGFR4/AMPK axis as a central driver of MASLD progression.

These findings identify circulating exosomal miR-122-3p as a promising non-invasive biomarker for MASLD. Targeting this miRNA or its downstream FGFR4 pathway may represent a novel therapeutic strategy to halt or reverse MASLD progression. The authors note that larger clinical cohorts are needed to validate these results and translate them into clinical applications.