Long-chain fatty acids induce lipid droplet formation in a cultured human hepatocyte in a manner dependent of acyl-CoA synthetase
Long-chain fatty acids induce lipid droplet formation in a cultured human hepatocyte in a manner dependent of acyl-CoA synthetase
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DOI：
10.1248/bpb.29.2174
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发表时间：
2006-11-01
影响因子：
2
通讯作者：
Takano, Tatsuya
中科院分区：
文献类型：
--
作者：
Fujimoto, Yasuyuki;Onoduka, Jun;Takano, Tatsuya
脂滴（LD）是中性脂质的细胞内储存位点，其在脂肪肝疾病中积聚。在这里，我们研究了脂肪酸和葡萄糖对LD形成的影响，在培养的人肝细胞，HuH 7，通过将它们添加到培养基中。含C12-C18糖链的脂肪酸可有效诱导LD，而C8和C10糖链的脂肪酸则无效。即使在胰岛素存在下，葡萄糖也不诱导LD形成。油酸诱导细胞中性脂质的显着增加，和细胞分级显示，大多数新合成的中性脂质集中在LD与LD蛋白。去除培养基葡萄糖不能消除LD形成，但ACSL抑制剂三胞苷C可显著抑制LD形成。这些结果表明，长链脂肪酸比葡萄糖更有助于LD形成，可能是通过被吸收到细胞中，被ACSL激活，重组为中性脂质，然后储存在LD中。孕烯醇酮和锂没有抑制油酸依赖性LD的形成，尽管以前的报告，他们的能力，以抑制LD形成的巨噬细胞和脂肪细胞之间的LD形成在这些细胞中的差异。
Lipid droplets (LDs) are intracellular storage sites of neutral lipids, which accumulate in fatty liver disease. Here, we investigated the effects of fatty acids and glucose on LD formation in a cultured human hepatocyte, HuH7, by adding them to culture media. Fatty acids with carbohydrate chains C12-C18 efficiently induced LDs, but those of C8 and C10 were ineffective. Glucose did not induce LD formation even in the presence of insulin. Oleic acid induced significant increases in cellular neutral lipids, and cell fractionation revealed that most of the newly synthesized neutral lipids were concentrated in LDs together with LD proteins. The LD formation was not abrogated by removal of medium glucose but was significantly inhibited by an ACSL inhibitor, triacsin C. These results demonstrate that long-chain fatty acids contribute to LD formation to a greater extent than glucose, possibly by being taken up into the cells, activated by ACSL, reconstituted into neutral lipids and then stored in LDs. Pregnenolone and lithium did not suppress oleic acid-dependent LD formation, despite previous reports of their ability to inhibit LD formation in macrophages and adipocytes suggesting differences among LD formations in these cells.