title: Effects of perfluorinated fatty acids with different carbon chain length on fatty acid profiles of hepatic lipids in mice.
abstract: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kudo
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Sunaga
authors.forename: Tadashi
authors.initials: T
authors.lastname: Tsuda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mitsumoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawashima
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000032:analysis; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002210:Caprylates / Q000032:analysis / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000032:analysis* / Q000096:biosynthesis / Q000737:chemistry / Q000633:toxicity*; D005229:Fatty Acids, Monounsaturated / Q000032:analysis; D005466:Fluorocarbons / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic; D006529:Hepatomegaly / Q000139:chemically induced* / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D050602:Linoleoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D019301:Oleic Acid / Q000032:analysis; D047493:PPAR alpha / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism
chemical_list: D002210:Caprylates; D004785:Environmental Pollutants; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005466:Fluorocarbons; D007527:Isoenzymes; D047493:PPAR alpha; D012333:RNA, Messenger; C008757:palmitoleic acid; D019301:Oleic Acid; C023036:perfluorooctanoic acid; D013230:Stearoyl-CoA Desaturase; D050602:Linoleoyl-CoA Desaturase; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D015126:8,11,14-Eicosatrienoic Acid