| Title: |
Extracellular Vesicles miRNome Profiling Reveals miRNAs Engagement in Dysfunctional Lipid Metabolism, Chronic Inflammation and Liver Damage in Subjects With Metabolic Dysfunction‐Associated Steatotic Liver Disease |
| Authors: |
Caviglia, Gian Paolo; Casalone, Elisabetta; Rosso, Chiara; Aneli, Serena; Allione, Alessandra; Carli, Fabrizia; Grange, Cristina; Armandi, Angelo; Catalano, Chiara; Birolo, Giovanni; Foglia, Beatrice; Ribaldone, Davide Giuseppe; Gastaldelli, Amalia; Matullo, Giuseppe; Bugianesi, Elisabetta |
| Contributors: |
Dipartimenti di Eccellenza; HORIZON EUROPE Framework Programme |
| Source: |
Alimentary Pharmacology & Therapeutics ; volume 62, issue 1, page 22-32 ; ISSN 0269-2813 1365-2036 |
| Publisher Information: |
Wiley |
| Publication Year: |
2025 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Background and Aims MicroRNAs (miRNAs) are short non‐coding oligonucleotides involved in the post‐transcriptional regulation of gene expression. We investigated the association between the miRNome profile of circulating extracellular vesicles (EVs) and metabolic derangements, circulating and hepatic pro‐inflammatory cytokines, and liver damage across the histological spectrum of metabolic dysfunction‐associated steatotic liver disease (MASLD). Methods EV miRNAs expression was determined by NGS (NextSeq550, Illumina Inc) in 228 biopsy‐proven MASLD patients. In vivo metabolic studies were performed in a subgroup of 54 patients by tracer infusion ([6,6‐ 2 H 2 ]glucose and [ 2 H 5 ]glycerol) to assess glucose and lipid fluxes and insulin resistance (IR) in the adipose tissue. Results Seven miRNAs (miR‐27b‐3p, miR‐30a‐5p, miR‐122‐5p, miR‐375‐3p, miR‐103a‐3p, let‐7d‐5p, and let‐7f‐5p) were differentially expressed according to the diagnosis of steatohepatitis and the presence of significant fibrosis ( F ≥ 2), thus marking subjects with ‘at‐risk MASH’. In the metabolic studies, the above‐reported miRNAs had the strongest associations with lipid metabolism: miR‐122‐5p and miR‐375‐3p levels directly correlated with circulating free fatty acids (FFAs) and adipose tissue (AT)‐IR, while let‐7d‐5p and let‐7f‐5p inversely correlated with lipolysis, FFAs, and progressively decreased according to AT‐IR severity. In addition, let‐7d‐5p and let‐7f‐5p inversely correlated with the circulating and hepatic expression of pro‐inflammatory cytokines, which increased by increasing degrees of AT‐IR. Conclusions Our results suggest an intertwined connection between miR‐122‐5p, miR‐375‐3p, and the let‐7 family in modulating lipid derangements and inflammatory pathways in patients with ‘at‐risk MASH’, paving the basis for further studies aiming at investigating their potential therapeutic value. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1111/apt.70150 |
| Availability: |
https://doi.org/10.1111/apt.70150; https://onlinelibrary.wiley.com/doi/pdf/10.1111/apt.70150 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.3C342BED |
| Database: |
BASE |