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Published on: July 18, 2019
Extracellular Vesicle-Based miRNA Profiling in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Secondary
Katja Lund Cliff1,2, Dominic Guanzon3,4, Andrew Lai3,4
1Department of Clinical Biochemistry Aalborg University Hospital Aalborg Denmark.
Abstract:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the worldwide leading cause of liver-related mortality with a prevalence of 75% among individuals with obesity and lacking screenings tools. Extracellular vesicles (EVs)-based microRNAs (miRNAs) have emerged as promising biomarkers with important roles in the pathogenesis of MASLD. This study aimed to characterize EV-based miRNA profiles in individuals with obesity and MASLD before and during weight loss intervention. Small RNA sequencing was used to profile EV-miRNAs from plasma across three groups: individuals with obesity and MASLD (n = 35), individuals with obesity without hepatic steatosis (n = 24) and lean controls without hepatic steatosis (n = 26). Further, the MASLD group underwent a personalized weight-loss intervention. The liver and MASLD-related miR-122-5p and three other miRNAs were differentially expressed in the MASLD group compared with the obesity control group at baseline. Moreover, miR-122-5p correlated with liver fat and liver enzymes (ALT, AST and GGT) at baseline, revealed solid predictability for MASLD in a combined panel (AUC = 0.8), and lastly demonstrated the highest accuracy in identifying individuals with high liver fat among all individuals with obesity. Finally, several MASLD- and hepatocellular carcinoma-related miRNAs decreased significantly following weight loss and liver fat reduction in the MASLD group.
Insights
Extracellular vesicle microRNAs show promise as biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD). Weight loss interventions reduced specific microRNAs linked to MASLD and liver fat.
Area of Science:
- * Hepatology and Molecular Biology
- * Biomarker Discovery
- * Metabolic Disease Research
Background:
- * Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of liver mortality, particularly in individuals with obesity.
- * Current screening tools for MASLD are lacking, highlighting the need for novel diagnostic approaches.
- * Extracellular vesicles (EVs)-based microRNAs (miRNAs) are implicated in MASLD pathogenesis and show potential as biomarkers.
Purpose of the Study:
- * To characterize EV-miRNA profiles in individuals with obesity and MASLD before and after a weight-loss intervention.
- * To identify specific EV-miRNAs associated with MASLD and liver fat content.
- * To assess the potential of EV-miRNAs as predictive biomarkers for MASLD.
Main Methods:
- * Small RNA sequencing was employed to profile EV-miRNAs from plasma samples.
- * Three groups were analyzed: MASLD with obesity (n=35), obesity without hepatic steatosis (n=24), and lean controls (n=26).
- * The MASLD group participated in a personalized weight-loss intervention.
Main Results:
- * Differential expression of miR-122-5p and three other miRNAs was observed in the MASLD group compared to obesity controls at baseline.
- * miR-122-5p correlated with liver fat and liver enzymes (ALT, AST, GGT), showing high predictability for MASLD (AUC=0.8).
- * Several MASLD- and hepatocellular carcinoma-related miRNAs significantly decreased after weight loss and reduction in liver fat.
Conclusions:
- * EV-derived miRNAs, particularly miR-122-5p, are promising biomarkers for MASLD diagnosis and assessing liver fat.
- * Weight loss interventions can modulate specific miRNA profiles associated with MASLD.
- * Further research into EV-miRNAs could lead to improved diagnostic and prognostic tools for MASLD.
