Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG2 cells: An in vitro model of non-alcoholic fatty liver disease
Open accessAbstract
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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HepG2 demonstrates a predictable steatogenic response to free fatty acids.
“HepG2 has been shown to demonstrate a predictable steatogenic response to free fatty acids (FFAs) and is convenient for reproducing early stages of pathogenesis and primary pharmacological selection of compounds.”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [85]
When treated with a mixture of free fatty acids (e.g., oleic acid + palmitic acid), HepG2 cells show significant triglyceride accumulation.
“When treated with a mixture of free fatty acids (e.g., oleic acid (OA) + palmitic acid (PA)), HepG2 cells show significant triglyceride accumulation [83,84,85].”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [85]
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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
- Publisher
- Spandidos Publications
- Published
- 2016-02-10
- Volume
- 11
- Issue
- 4
- Pages
- 1487-1492
- ISSN
- 1792-0981 (ISSN-L)
- 1792-1015
- PMC
- PMC4812233
- 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
- diamond
- doi.org
- 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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