| Interruption of triacylglycerol synthesis in the endoplasmic reticulum is the initiating event for saturated fatty acid-induced lipotoxicity in liver cells. | |
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MedLine Citation:
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PMID: 21182590 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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The aim of the present study was to investigate in detail the molecular mechanisms by which free fatty acids induce liver toxicity in liver cells. HepG2 and Huh7 human liver cell lines were exposed to varying concentrations of stearate (18:0), oleate (18:1), or mixtures of the two fatty acids, and the effects on cell proliferation, lipid droplet accumulation and induction of endoplasmic reticulum stress and apoptosis were evaluated. It was observed that: (a) stearate, but not oleate, inhibited cell proliferation and induced cell death; (b) stearate-induced cell death had the characteristics of endoplasmic reticulum stress-mediated and mitochondrial-mediated apoptosis; (c) the activation of stearate in the form of stearoyl-CoA was a necessary step for the lipotoxic effect; (d) the capacity of cells to produce and accumulate triacylglycerols in the form of lipid droplets was interrupted following exposure to stearate, whereas it proceeded normally in oleate-treated cells; and (e) the presence of relatively low amounts of oleate protected cells from stearate-induced toxicity and restored the ability of the cells to accumulate triacylglycerols. Our data suggest that interruption of triacylglycerol synthesis in the endoplasmic reticulum, apparently because of the formation of a pool of oversaturated intermediates, represents the key initiating event in the mechanism of saturated fatty acid-induced lipotoxicity. |
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Authors:
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Michalis D Mantzaris; Epameinondas V Tsianos; Dimitrios Galaris |
Publication Detail:
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Type: Journal Article Date: 2010-12-23 |
Journal Detail:
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Title: The FEBS journal Volume: 278 ISSN: 1742-4658 ISO Abbreviation: FEBS J. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101229646 Medline TA: FEBS J Country: England |
Other Details:
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Languages: eng Pagination: 519-30 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors Journal compilation © 2010 FEBS. |
Affiliation:
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Laboratory of Biological Chemistry, University of Ioannina Medical School, Greece First Division of Internal Medicine and Hepato-gastroenterology Unit, University of Ioannina Medical School, Greece. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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