Effects of Perfluorinated Fatty Acids with Different Carbon Chain Length on Fatty Acid Profiles of Hepatic Lipids in Mice

• Published in: Biological & pharmaceutical bulletin Vol. 34; no. 6; pp. 856 - 864
• Main Authors: Kudo, Naomi, Yamazaki, Tohru, Sakamoto, Takeshi, Sunaga, Katsuyoshi, Tsuda, Tadashi, Mitsumoto, Atsushi, Kawashima, Yoichi
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.06.2011; Japan Science and Technology Agency
• Subjects: 8,11,14-Eicosatrienoic Acid - analysis; Acetyltransferases - genetics; Acetyltransferases - metabolism; Animals; Caprylates - analysis; Caprylates - toxicity; carbon chain length; Dose-Response Relationship, Drug; Environmental Pollutants - analysis; Environmental Pollutants - chemistry; Environmental Pollutants - toxicity; fatty acid profile; Fatty Acids - analysis; Fatty Acids - biosynthesis; Fatty Acids - chemistry; Fatty Acids - toxicity; Fatty Acids, Monounsaturated - analysis; Fluorocarbons - analysis; Fluorocarbons - chemistry; Fluorocarbons - toxicity; Gene Expression Regulation, Enzymologic; Hepatomegaly - chemically induced; Hepatomegaly - metabolism; Isoenzymes - genetics; Isoenzymes - metabolism; Linoleoyl-CoA Desaturase - genetics; Linoleoyl-CoA Desaturase - metabolism; Liver - chemistry; Liver - drug effects; Liver - metabolism; liver lipid; Male; Mice; Mice, Inbred Strains; Molecular Weight; mouse; Oleic Acid - analysis; perfluorinated fatty acid; PPAR alpha - metabolism; RNA, Messenger - metabolism; stearoyl-CoA desaturase; Stearoyl-CoA Desaturase - genetics; Stearoyl-CoA Desaturase - metabolism
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.34.856

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), Δ6 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 novo fatty acid synthesis, chain elongase and Δ6 desaturase and (iii) that the mechanism underlying SCD induction is, in part, mediated through peroxisome proliferator-activated receptor α.