Cited by 44Liver Disease Diagnosis and TreatmentCancer, Lipids, and MetabolismDrug-Induced Hepatotoxicity and Protection

Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG2 cells: An in vitro model of non-alcoholic fatty liver disease

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ALKHATATBEH, MOHAMMAD J., LINCZ, LISA F., THORNE, RICK F.·2016·Experimental and Therapeutic Medicine

Abstract

Non-alcoholic fatty liver disease (NAFLD) is an inflammatory condition caused by hepatic lipid accumulation that is associated with insulin resistance, diabetes and metabolic syndrome. Although statins should be used with caution in liver diseases, they are increasingly investigated as a possible treatment for NAFLD. The present study recreated an in vitro model of NAFLD using HepG2 cells exposed to oleic acid (OA), which was used to quantify OA-induced lipid accumulation in HepG2 cells treated with various concentrations of simvastatin. In addition, the effect of simvastatin on HepG2 cell morphology and microparticle generation as a marker of cell apoptosis was assessed. OA‑induced lipid accumulation was quantified by Oil Red O staining and extraction for optical density determination. Stained lipid droplets were visualized using phase contrast microscopy. Furthermore, HepG2 cell‑derived microparticles were counted by flow cytometry subsequent to staining for Annexin V. HepG2 cells treated with 0‑1 mM OA showed dose‑dependent lipid accumulation. Treatment of HepG2 cells with increasing concentrations of simvastatin followed by treatment with 1 mM OA showed that low simvastatin concentrations (4‑10 µM) were able to reduce lipid accumulation by ~40%, whereas high simvastatin concentrations (20 and 30 µM) induced apoptotic changes in cell morphology and increased the production of Annexin V+ microparticles. This suggests that low simvastatin doses may have a role in preventing NAFLD. However, further investigations are required to confirm this action in vivo and to determine the underlying mechanism by which simvastatin reduces hepatic steatosis.

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Registry

Crossref · 10.3892/etm.2016.3069

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34 of 34 references verified0 citation errors · 0 not checkable

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Authors
ALKHATATBEH, M. J., LINCZ, L. F., & THORNE, R. F.
Affiliations
  • Jordan University of Science and Technology (JO)
  • Calvary Mater Newcastle Hospital (AU)
  • University of Newcastle Australia (AU)
Venue
Experimental and Therapeutic Medicine
Published
2016-02-10
Volume
11
Issue
4
Pages
1487-1492
ISSN
  • 1792-0981 (ISSN-L)
  • 1792-1015
OpenAlex
W2257821188
Cited by
44
References
35
Citations by year
2026: 7 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 1 · 2016: 2
FWCI
2.50
Type
journal article
Language
en
Open access
Locations
  • Experimental and Therapeutic Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
simvastatin, non-alcoholic fatty liver disease, hepatic steatosis, oleic acid, HepG2 cells, lipid accumulation, statins, apoptosis, microparticles, annexin V, dose-dependent effects

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