Enhanced oleate uptake and lipotoxicity associated with laurate.
Enhanced oleate uptake and lipotoxicity associated with laurate.
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DOI：
10.1016/j.fob.2015.05.008
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发表时间：
2015
期刊：
影响因子：
2.6
通讯作者：
Shimomura, Yoshiharu
中科院分区：
文献类型：
--
作者：
Kitaura, Yasuyuki;Inoue, Kana;Kato, Naoki;Matsushita, Nahomi;Shimomura, Yoshiharu
月桂酸盐和油酸盐的组合可协同增强脂毒性。受油酸和月桂酸组合影响的细胞死亡途径因细胞类型而异。月桂酸增加油酸的吸收。据报道，游离脂肪酸会诱导细胞死亡（脂毒性），但其效果取决于碳链长度和双键数量。中链饱和脂肪酸（MC-SFA），例如月桂酸酯，比长链饱和脂肪酸（LC-SFA），例如棕榈酸酯，具有较小的脂毒性。据报道，单不饱和脂肪酸（例如油酸）不仅可以发挥细胞毒性作用，还可以降低 LC-SFA 的脂毒性。然而，MC-SFA 和油酸盐在细胞死亡方面的相互作用尚不清楚。在这份报告中，我们发现，相对于单独的脂肪酸，月桂酸酯和油酸酯的组合增强了脂毒性。通过测量活性氧的产生、线粒体去极化、caspase-3 活性和脂滴形成来检查所涉及的可能机制。尽管不同细胞类型之间的应激信号和细胞死亡途径不同，但我们发现所有测试的细胞中脂滴形成增强的常见现象。使用荧光或放射性同位素标记的脂肪酸，我们发现油酸盐（而不是月桂酸盐）增加了荧光标记脂肪酸的摄取，并且组合效应比单独使用油酸盐更有效。我们还发现月桂酸增加了油酸的摄取，但油酸对月桂酸摄取的影响因细胞类型而异。这些结果表明，月桂酸盐提高了油酸的流入速率，其细胞内浓度的增加不仅增强了脂质储存，而且还通过脂毒性应激反应诱导细胞死亡，这根据细胞类型而变化。
A combination of laurate and oleate synergistically enhances lipotoxicity. Cell death pathways influenced by a combination of oleate and laurate vary among cell types. Laurate increases oleate uptake. 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.
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影响因子：
25.7
作者：
Akazawa Y;Cazanave S;Mott JL;Elmi N;Bronk SF;Kohno S;Charlton MR;Gores GJ
通讯作者：
Gores GJ
影响因子：
4.8
作者：
Listenberger, LL;Ory, DS;Schaffer, JE
通讯作者：
Schaffer, JE
影响因子：
6.5
作者：
Leamy, Alexandra K.;Egnatchik, Robert A.;Young, Jamey D.
通讯作者：
Young, Jamey D.
DOI：
10.1152/ajpgi.00386.2005
发表时间：
2006-03-01
影响因子：
4.5
作者：
Guo, W;Huang, N;Hamilton, JA
通讯作者：
Hamilton, JA
DOI：
10.1111/j.1440-1746.2008.05733.x
发表时间：
2009-05-01
影响因子：
4.1
作者：
Ricchi, Matteo;Odoardi, Maria Rosaria;Loria, Paola
通讯作者：
Loria, Paola