title: Enhanced oleate uptake and lipotoxicity associated with laurate.
abstract: Free fatty acids have been reported to induce cell death (lipotoxicity), but the effects depend on the carbon chain length and number of double bonds. Medium-chain saturated fatty acids (MC-SFAs), such as laurate, have less lipotoxicity than long-chain saturated fatty acids (LC-SFAs), such as palmitate. Monounsaturated fatty acids, such as oleate, have also been reported not only to exert cytotoxic effects, but also to reduce the lipotoxicity of LC-SFA. However the interaction between MC-SFA and oleate with respect to cell death is unclear. In this report, we found that lipotoxicity was enhanced by a combination of laurate and oleate relative to either fatty acid alone. The possible mechanisms involved were examined by measuring the production of reactive oxygen species, mitochondrial depolarization, caspase-3 activity, and lipid droplet formation. Although the stress signals and cell death pathways were distinct among different cell types, we found a common phenomenon of enhanced lipid droplet formation in all cells tested. Using fluorescent- or radioisotope-labeled fatty acids, we found that oleate, but not laurate, increased the uptake of fluorescent-labeled fatty acids, and the combinatory effect was more efficient than with oleate alone. We also found that laurate increased oleate uptake, but the effect of oleate on laurate uptake varied among cell types. These results suggest that laurate enhances the influx rate of oleate, the increased intracellular concentration of which not only enhances lipid storage, but also induces cell death by lipotoxic stress responses, which vary according to cell type.
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kitaura
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kato
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan.
authors.forename: Nahomi
authors.initials: N
authors.lastname: Matsushita
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Shimomura
keywords: Fatty acid; LC-SFAs, long-chain saturated fatty acids; Laurate; Lipotoxicity; MC-SFAs, medium-chain saturated fatty acids; Oleate; ROS, reactive oxygen species; SFAs, saturated fatty acids; TG, triacylglycerol