Study on the variety of the effects of perfluorinated fatty acids on biological systems and the biological mechanisms for identification of each molecules.

在大鼠中比较了具有7-10个碳原子的全氟脂肪酸（PFCAs）的作用。含有8-10个碳原子的PFCAs降低了血清脂质水平。含有9和10个碳原子的PFCA引起大鼠肝和肾近端小管细胞脂滴积聚。在含有10个碳原子的PFCA处理的大鼠肝脏中，脂肪酸合成和β-氧化加速，而VLDL的分泌受到抑制。因此，甘油三酯（TG）的积累被认为至少部分是由于抑制VLDL分泌和加速脂肪酸合成。比较PFCA诱导大鼠肝脏过氧化物酶体β-氧化和TG积累的效力，碳链长度较长的PFCA更有效。在具有8和9个碳原子的PFCAs的影响中观察到与性别相关的差异。无论PFCA的碳链长度如何，肝脏中PFCA浓度与过氧化物酶体β-氧化活性或肝脏TG含量之间存在高度显著的相关性，提示肝脏中积累的差异是诱导大鼠过氧化物酶体β-氧化和TG积累的效力不同的原因。从小鼠身上也得到了基本相同的结果。碳链长度较短的PFCA更快地排泄到尿液中。雌性大鼠排出PFCA的速度比雄性大鼠快。而PFCAs在粪便中的排泄速度较尿液慢，且不同碳链长度的PFCAs在性别间无显著差异。雄性大鼠尿排泄率受睾酮调节。结果表明，具有7-9个碳原子的PFCAs之间的积累差异是由于尿排泄速率的差异，而尿排泄速率是由睾酮调节的。

The effects of perfluorinated fatty acids (PFCAs) having 7-10 carbon atoms were compared in rats. PFCAs having 8-10 carbon atoms lowered serum levels of lipids. PFCA having 9 and 10 carbon atoms caused accumulation of lipid droplets in the liver and renal proximal tubular cells in rats.In the liver of rats treated with PFCA having 10 carbon atoms, fatty acid synthesis and β-oxidation was accelerated whereas secretion of VLDL was suppressed. Therefore, the accumulation of triglyceride (TG) is thought to be, at least partly, due to suppression of VLDL secretion and acceleration of fatty acid synthesis.When the potency of the induction of peroxisomal β-oxidation and accumulation of TG in rat liver was compared, PFCA having longer carbon chain length was more potent. Sex-related difference was observed in the effects of PFCAs having 8 and 9 carbon atoms. There are highly significant correlations between hepatic concentrations of PFCA and the activity of peroxisomal β-oxidation or hepatic TG content regardless of the carbon chain length of PFCA, suggesting that difference in the accumulation in liver is responsible for the difference in the potency of the induction of peroxisomal β-oxidation and TG accumulation in rats. Essentially the same result was obtained from mice.PFCA having shorter carbon chain length was more quickly excreted into urine. Female rats excreted PFCA faster than male rats. By contrast, excretion rates of PFCAs in feces were slow compared to those of urine and there was no significant difference between PFCAs having different carbon chain length and between sexes. Urinary excretion rate was regulated by testosterone in male rats. The results indicate that the difference in the accumulation between PFCAs having 7-9 carbon atoms is due to difference in the rate of urinary excretion, which is regulated by testosterone.