Effects of Perfluorinated Fatty Acids with Different Carbon Chain Length on Fatty Acid Profiles of Hepatic Lipids in Mice
Effects of Perfluorinated Fatty Acids with Different Carbon Chain Length on Fatty Acid Profiles of Hepatic Lipids in Mice
复制标题
DOI：
10.1248/bpb.34.856
复制
发表时间：
2011-06-01
影响因子：
2
通讯作者：
Kawashima, Yoichi
中科院分区：
文献类型：
--
作者：
Kudo, Naomi;Yamazaki, Tohru;Kawashima, Yoichi
研究了链长为6~9个碳的全氟化脂肪酸(PFCA)对小鼠肝脏脂肪酸谱的影响。所有PFCA引起的特征性变化是肝脂中油酸(18：1)、棕榈油酸(16：1)和8，11，14-二十碳三烯酸(20：3)的含量和比例增加。经PFCAs处理后，肝脏中棕榈酸的含量也有所增加。这些影响几乎依赖于肝脏中PFCA分子的浓度，而与其碳链长度无关。全氟辛酸使乙酰辅酶A羧基酶、脂肪酸合成酶、苹果酸酶、硬脂酰辅酶A脱饱和酶(SCD)(SCD 1和2)、链延长酶(ELOVL5)、Delta 6脱饱和酶(FADS2)、1-酰基甘油磷胆碱酰基转移酶(LPCAT3)的mRNA表达增加。这四种PFCA以肝脏浓度依赖的方式诱导微粒体SCD和LPCAT，而与碳链长度无关。在较宽的浓度范围内，LPCAT活性与PFCA的肝脏浓度呈线性回归关系，而在相对较低的浓度下，SCD的诱导是饱和的。这些结果表明：(I)链长度为6-9碳的PFCA通过增加16：1、18：1和20：3的含量和比例来改变肝脂的脂肪酸组成，(Ii)这些脂肪酸组成的改变是由于SCD、De-nova脂肪酸合成、链延长酶和Delta 6脱饱和酶的上调所引起的，(Iii)SCD诱导的机制部分是通过过氧化物酶体增殖物激活的受体α介导的。
Alterations by perfluorinated fatty acids (PFCAs) with a chain length of 6-9 carbons in the fatty acid profile of hepatic lipids of mice were investigated. The characteristic changes caused by all the PFCAs examined were increases in the contents and proportions of oleic acid (18: 1), palmitoleic acid (16: 1) and 8,11,14-eicosatrienoic acid (20: 3) in hepatic lipids. Hepatic contents of palmitic acid were also increased by the treatments with the PFCAs. These effects were almost dependent on the hepatic concentrations of PFCA molecules regardless of their carbon chain length. Perfluorooctanoic acid elevated the expressions of mRNA encoding acetyl-CoA carboxylase, fatty acid synthase, malic enzyme, stearoyl-CoA desaturase (SCD) (SCD1 and 2), chain elongase (ELOVL5), Delta 6 desaturase (Fads2), 1-acylglycerophosphocholine acyltransferase (LPCAT) (LPCAT3). The four PFCAs examined induced microsomal SCD and LPCAT in hepatic concentration-dependent manners regardless of carbon chain length. One linear regression line was confirmed between LPCAT activity and hepatic concentration of PFCA at wide range of the concentration, whereas the induction of SCD was saturable at relatively low concentration of PFCAs. These results suggest (i) that PFCAs with a chain length of 6-9 carbons change the fatty acid profile of hepatic lipids by increasing contents and proportions of 16: 1, 18: 1 and 20 : 3, (ii) that these alterations in fatty acid profile are caused by up-regulation of SCD, de nova fatty acid synthesis, chain elongase and Delta 6 desaturase and (iii) that the mechanism underlying SCD induction is, in part, mediated through peroxisome proliferator-activated receptor alpha.