Effects of chronic administration of perfluorooctanoic acid on fatty acid metabolism in rat liver: relationship among stearoyl-coenzyme A desaturase, 1-acylglycerophosphocholine acyltransferase, and acyl composition of microsomal phosphatidylcholine.
Male and female rats were fed on a diet containing 0.01% (w/w) perfluorooctanoic acid (PFOA) for 2, 22, or 26 weeks and effect of PFOA on activities of microsomal 1-acylglycerophosphocholine acyltransferase, microsomal stearoyl-coenzyme A (CoA) desaturase, peroxisomal beta-oxidation and on acyl composition of microsomal phosphatidylcholine in liver were studied. The treatment of male rats with PFOA for 2 weeks caused increases in the activities of stearoyl-CoA desaturase, 1-acylglycerophosphocholine acyltransferase, and peroxisomal beta-oxidation. The elevated activities of microsomal 1-acylglycerophosphocholine acyltransferase and peroxisomal beta-oxidation were unchanging throughout the long-term treatment. The induced activity of microsomal 1-acylglycerophosphocholine acyltransferase was found to be highly correlated with the induced activity of peroxisomal beta-oxidation. In contrast to these two enzymes, the increased activity of stearoyl-CoA desaturase by the short-term treatment of rats with PFOA did not last for 26 weeks, although the activity in rats treated for the long-term was higher than that of age-matched controls. The treatment of male rats with PFOA caused great alterations in the acyl composition of microsomal phosphatidylcholine. The high correlation seen between proportion of 18:1 in the C-2 position of phosphatidylcholine and activities of both stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase suggest that these two enzymes participate actively in the regulation of acyl composition of phosphatidylcholine in rat liver. The present results show that hepatic responses to PFOA remain consistent throughout the period of the administration, but the elevated activities of the hepatic enzymes and the altered acyl composition of microsomal phosphatidylcholine returned to control levels within 4 weeks after PFOA was withdrawn from the diet. Even after the chronic administration of PFOA, these parameters of female rats responded only slightly to the challenges by the chemical, which indicates a marked sex-related difference being still apparent in the response of rat liver to PFOA.
Uy-Yu
N
N
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Kawashima
Y
Y
Horii
S
S
Kozuka
H
H
D008243:1-Acylglycerophosphocholine O-Acyltransferase; D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005466:Fluorocarbons / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism*; D013997:Time Factors
D002210:Caprylates; D005227:Fatty Acids; D005466:Fluorocarbons; D010713:Phosphatidylcholines; C023036:perfluorooctanoic acid; D013230:Stearoyl-CoA Desaturase; D000217:Acyltransferases; D008243:1-Acylglycerophosphocholine O-Acyltransferase