longevity nutrition

Consolidating Clinical Insights and Uncovering Novel Regulatory Mechanisms of Exosomal MicroRNAs in Obesity and Metabolic Dysfunction Associated Steatotic Liver Disease: A Systematic Review and Bioinformatics Analysis

22 May 2026

Mo Q, Ghafourian A, Hamdi M, Alidadipour A, Soleimani M, Davoudi M, Miao X, Afrisham R, Bagherieh M.

Summary

What the study found

This research identifies specific tiny molecular messengers called exosomal miRNAs that facilitate communication between body fat and the liver. It demonstrates that obesity and fatty liver disease share deep genetic pathways, explaining how fat tissue directly sends signals that trigger liver inflammation and metabolic dysfunction.

Key findings

Researchers identified shared regulatory networks between obesity and fatty liver disease, specifically highlighting let-7b and miR-335-5p as critical bridges between the two conditions.
Certain molecular markers like miR-298 and miR-342 demonstrated superior diagnostic accuracy for liver dysfunction compared to traditional blood tests like alanine aminotransferase (ALT).
The protein adiponectin (ADIPOQ) emerged as a central therapeutic target, suggesting that maintaining healthy fat tissue signaling is essential for protecting the liver.
Signals derived from body fat, such as miR-122 and miR-192, were consistently linked to liver cell damage and systemic inflammation.

Practical takeaways

This study highlights that managing obesity is not just about weight loss, but about silencing harmful molecular "crosstalk" that damages internal organs. Strategies that improve fat tissue health, such as consistent physical activity and anti-inflammatory nutrition, may help protect the liver by modulating these genetic messengers.

Limitations

The findings rely heavily on bioinformatics and computational modeling, which must be confirmed through more extensive human clinical trials. Furthermore, testing for these specific exosomal markers is currently a specialized laboratory technique and not yet available for routine medical screenings.

Abstract

Obesity and metabolic dysfunction associated steatotic liver disease (MASLD) are interrelated metabolic disorders characterized by chronic inflammation, insulin resistance, and dyslipidemia. While both conditions are well recognized clinically, the molecular mechanisms underlying their frequent coexistence remain poorly understood. Growing evidence indicates that circulatory exosomal microRNAs (miRNAs) act as critical mediators of inter-organ communication. In this PROSPERO-registered systematic review (CRD420251017335), we integrated clinical evidence with bioinformatics analyses to clarify shared miRNA-mediated regulatory networks between obesity and MASLD. Literature was retrieved from MEDLINE, ISI Web of Science, and Embase. Bioinformatics analysis using miRWalk also revealed shared miRNAs, predicted target genes, and elucidated enriched pathways using Gene Ontology and KEGG. Clinical studies identified 93 obesity-associated and 24 MASLD-associated exosomal miRNAs, with let-7b and miR-335-5p emerging as common nodes. Bioinformatics analysis using miRWalk revealed extensive overlap at the functional level, including 40,410 shared miRNA-mRNA interactions and 42 common target genes. Several circulating exosomal miRNAs from obese individuals, including miR-122, miR-192, miR-128, and miR-9-5p, were consistently associated with liver histopathology, inflammatory markers, and liver enzyme levels. Importantly, obesity-derived miR-298, miR-342, and let-7d-5p showed strong diagnostic performance (AUC ≥ 0.85), exceeding that of alanine aminotransferase (ALT). Furthermore, ADIPOQ emerged as a central therapeutic target within the shared miRNA network, regulated by both let-7b and miR-335-5p, providing a molecular link between adipose tissue dysfunction and hepatic metabolic regulation. This integrative analysis supports a unified model in which exosomal miRNAs serve as key molecular intermediaries connecting obesity and MASLD.

Source study →