A research team from Shandong First Medical University in China reports on Apr. 17 that circulating exosomal microRNAs, particularly miR-122-3p, could be a promising non-invasive biomarker for metabolic dysfunction-associated steatotic liver disease (MASLD). The findings were published in the Chinese Medical Journal on March 16.
MASLD is a growing public health concern worldwide, with its prevalence increasing rapidly, especially in China. Despite recent advances in treatment options, researchers say the molecular mechanisms underlying the disease are not fully understood.
The study involved collecting plasma samples from six patients with MASLD and six healthy volunteers. After isolating and analyzing exosomes from these samples, the researchers found that levels of miR-122-3p and miR-3614-5p were significantly higher in patients compared to controls. Further laboratory experiments showed that only miR-122-3p led to triglyceride buildup and increased reactive oxygen species—both key features of MASLD—in liver cell models.
Additional tests revealed that exosomes engineered to overexpress miR-122-3p produced similar pathological effects by suppressing adenosine 5'-monophosphate-activated protein kinase (AMPK) activity, which normally helps protect against fatty liver changes. The team also identified fibroblast growth factor receptor 4 (FGFR4) as a direct target of miR-122-3p; when FGFR4 was overexpressed, it reversed much of the damage caused by high levels of this microRNA.
The authors say their results validate the importance of the miR-122-3p/FGFR4/AMPK pathway in driving MASLD progression. They suggest that targeting this pathway could lead to new treatments for the disease but caution that larger clinical studies are needed before these findings can be applied in practice.
