- Title
- Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG₂ cells: an in vitro model of non-alcoholic fatty liver disease
- Creator
- Alkhatatbeh, Mohammad J.; Lincz, Lisa F.; Thorne, Rick F.
- Relation
- Experimental and Therapeutic Medicine Vol. 11, Issue 4, p. 1487-1492
- Publisher Link
- http://dx.doi.org/10.3892/etm.2016.3069
- Publisher
- Spandidos Publications
- Resource Type
- journal article
- Date
- 2016
- Description
- 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 concen- trations (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.
- Subject
- non‑alcoholic fatty liver disease; oleic acid; simvastatin; steatosis; microparticles
- Identifier
- http://hdl.handle.net/1959.13/1322877
- Identifier
- uon:24678
- Identifier
- ISSN:1792-0981
- Language
- eng
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