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Updated: May 11, 2026

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
Expression of genes for microRNA-processing enzymes is altered in advanced non-alcoholic fatty liver disease
Haveesh Sharma1, Michael Estep, Aybike Birerdinc
1Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia 22042, USA.
Background And Aim:
Recently, microRNAs (miRNA) have been linked to the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH). First transcribed as pri-miRNA, these molecules are further processed by a complex of endonuclear and cytosolic RNA binding molecules to form mature miRNAs. The aim of this study is to investigate mechanisms of miRNA regulation in the visceral adipose of obese NAFLD patients via measuring expression of miRNA processing enzymes and pri-miRNA.
Methods:
Total RNAs were extracted from visceral adipose tissue (VAT) samples collected from patients undergoing bariatric surgery. All patients had biopsy-proven NAFLD (NASH patients [n = 12] and non-NASH NAFLD [n = 12]). For each patient, we profiled mRNA levels for three miRNA processing elements (Drosha, DGCR8, and Dicer1) and seven pri-miRNAs (pri-miR-125b-2, pri-miR-16-2, pri-miR-26a-1, pri-miR-26a-2, pri-miR-7-1, pri-miR-7-2, and pri-miR-7-3).
Results:
Expression of Dicer1, Drosha and DGCR8 was significantly increased within the NASH cohort along with expression of pri-miR-7-1. The presence of focal necrosis on the liver biopsy correlated significantly with levels of Dicer1 and DGRC8. Both NASH and ballooning degeneration of hepatocytes correlated negatively with the expression levels of hsa-miR-125b. Histologic NASH correlated positively with the expression levels of pri-miR-16-2 and pri-miR-7-1. The presence of the hepatocyte's ballooning degeneration in the liver biopsy correlated positively with pri-miR-26a-1 and pri-miR-7-1. The expression profile of pri-miR-125b-2 also correlated positively with body mass index.
Conclusions:
Our findings support the hypothesis that VAT-derived miRNA may contribute to the pathogenesis of NASH in obese patients.
Insights
Visceral adipose tissue microRNAs (miRNAs) and their processing enzymes are altered in non-alcoholic steatohepatitis (NASH). These changes suggest a role for adipose-derived miRNAs in NASH pathogenesis in obese patients.
Area of Science:
- Molecular biology
- Gastroenterology
- Endocrinology
Background:
- MicroRNAs (miRNAs) are implicated in the development and progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH).
- miRNAs are transcribed as pri-miRNAs and processed by specific enzymes into mature forms.
- Understanding miRNA regulation in visceral adipose tissue (VAT) is crucial for NAFLD/NASH research.
Purpose of the Study:
- To investigate miRNA processing enzyme and pri-miRNA expression in VAT of obese patients with NAFLD.
- To explore the relationship between miRNA regulation and NAFLD/NASH severity.
Main Methods:
- VAT samples were collected from bariatric surgery patients with biopsy-proven NAFLD (NASH [n=12] and non-NASH [n=12]).
- mRNA levels of miRNA processing enzymes (Drosha, DGCR8, Dicer1) and specific pri-miRNAs were measured.
- Correlations with liver histology and body mass index were analyzed.
Main Results:
- NASH patients showed increased expression of Dicer1, Drosha, DGCR8, and pri-miR-7-1.
- Focal necrosis correlated with Dicer1 and DGCR8 levels.
- Hepatocyte ballooning degeneration correlated positively with pri-miR-26a-1 and pri-miR-7-1.
- Histologic NASH correlated positively with pri-miR-16-2 and pri-miR-7-1.
- pri-miR-125b-2 expression correlated positively with BMI.
Conclusions:
- Elevated expression of miRNA processing enzymes and specific pri-miRNAs in VAT is associated with NASH.
- These findings support the role of VAT-derived miRNAs in the pathogenesis of NASH in obese individuals.
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