TAILIEUCHUNG - Báo cáo khoa học: Interruption of triacylglycerol synthesis in the endoplasmic reticulum is the initiating event for saturated fatty acid-induced lipotoxicity in liver cells

The aim of the present study was to investigate in detail the molecular mecha-nisms by which free fatty acids induce liver toxicity in liver cells. HepG2 and Huh7 human liver cell lines were exposed to varying concentrations of stea-rate (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. | IFEBS Journal Interruption of triacylglycerol synthesis in the endoplasmic reticulum is the initiating event for saturated fatty acid-induced lipotoxicity in liver cells Michalis D. Mantzaris1 Epameinondas V. Tsianos2 and Dimitrios Galaris1 1 Laboratory of BiologicalChemistry University of loannina MedicalSchool Greece 2 First Division of InternalMedicine and Hepato-gastroenterology Unit University of Ioannina Medical School Greece Keywords endoplasmic reticulum stress lipoapoptosis nonalcoholic fatty liver disease NAFLD oleate stearate Correspondence D. Galaris Laboratory of Biological Chemistry University of Ioannina Medical School 451 10 Ioannina Greece Fax 30 26510 07868 Tel 30 26510 07562 E-mail dgalaris@ Received 14 October 2010 revised 16 November 2010 accepted 24 November 2010 doi 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 .

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