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
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| Natura: | Artículo Open Access |
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Wiley
2025
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| author | Gian Paolo Caviglia Elisabetta Casalone Chiara Rosso Serena Aneli Alessandra Allione Fabrizia Carli Cristina Grange Angelo Armandi Chiara Catalano Giovanni Birolo Beatrice Foglia Davide Giuseppe Ribaldone Amalia Gastaldelli Giuseppe Matullo Elisabetta Bugianesi |
| author_facet | Gian Paolo Caviglia Elisabetta Casalone Chiara Rosso Serena Aneli Alessandra Allione Fabrizia Carli Cristina Grange Angelo Armandi Chiara Catalano Giovanni Birolo Beatrice Foglia Davide Giuseppe Ribaldone Amalia Gastaldelli Giuseppe Matullo Elisabetta Bugianesi Gian Paolo Caviglia Elisabetta Casalone Chiara Rosso Serena Aneli Alessandra Allione Fabrizia Carli Cristina Grange Angelo Armandi Chiara Catalano Giovanni Birolo Beatrice Foglia Davide Giuseppe Ribaldone Amalia Gastaldelli Giuseppe Matullo Elisabetta Bugianesi |
| collection | Wiley Open Access |
| contents | 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 Gian Paolo Caviglia Elisabetta Casalone Chiara Rosso Serena Aneli Alessandra Allione Fabrizia Carli Cristina Grange Angelo Armandi Chiara Catalano Giovanni Birolo Beatrice Foglia Davide Giuseppe Ribaldone Amalia Gastaldelli Giuseppe Matullo Elisabetta Bugianesi Alimentary Pharmacology & Therapeutics ABSTRACTBackground and AimsMicroRNAs (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).MethodsEV 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 ([6,6‐2H2]glucose and [2H5]glycerol) to assess glucose and lipid fluxes and insulin resistance (IR) in the adipose tissue.ResultsSeven 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.ConclusionsOur 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. 10.1111/apt.70150 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1111/apt.70150 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_apt_70150 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | 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 Gian Paolo Caviglia Elisabetta Casalone Chiara Rosso Serena Aneli Alessandra Allione Fabrizia Carli Cristina Grange Angelo Armandi Chiara Catalano Giovanni Birolo Beatrice Foglia Davide Giuseppe Ribaldone Amalia Gastaldelli Giuseppe Matullo Elisabetta Bugianesi Alimentary Pharmacology & Therapeutics 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 Gian Paolo Caviglia Elisabetta Casalone Chiara Rosso Serena Aneli Alessandra Allione Fabrizia Carli Cristina Grange Angelo Armandi Chiara Catalano Giovanni Birolo Beatrice Foglia Davide Giuseppe Ribaldone Amalia Gastaldelli Giuseppe Matullo Elisabetta Bugianesi Alimentary Pharmacology & Therapeutics ABSTRACTBackground and AimsMicroRNAs (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).MethodsEV 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 ([6,6‐2H2]glucose and [2H5]glycerol) to assess glucose and lipid fluxes and insulin resistance (IR) in the adipose tissue.ResultsSeven 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.ConclusionsOur 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. 10.1111/apt.70150 http://creativecommons.org/licenses/by/4.0/ |
| 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 |
| topic | Alimentary Pharmacology & Therapeutics |
| url | https://onlinelibrary.wiley.com/doi/10.1111/apt.70150 |