Fish oil-feeding prevents perfluorooctanoic acid-induced fatty liver in mice.

The effects of perfluorooctanoic acid (PFOA) on the levels of lipids in liver and serum were compared between mice fed a diet supplemented with soy bean oil (SO), perilla oil (PO), or fish oil (FO) for 4 weeks. Hepatic content of triglyceride (TG) was significantly lower in the mice fed the FO diet than that in the mice fed either the SO or the PO diet. The treatment with PFOA caused a marked accumulation of TG in the livers of SO-fed and PO-fed mice (seven- and twofold over their respective controls), whereas a level of TG remained low in the mice fed the FO diet. Incorporation in vivo of [3H]glycerol revealed that FO-feeding reduced synthesis of TG in the liver. The administration of PFOA increased the incorporation of [3H]glycerol into hepatic phospholipid (PL) regardless of the dietary oil, while synthesis of hepatic TG from [3H]glycerol was not altered by the treatment with PFOA. Serum level of TG was reduced by the administration of PFOA to the mice fed either the SO diet or the PO diet, while no change in the level was observed in the mice fed the FO diet. These results suggest that the accumulation of TG in the livers of PFOA-treated mice is due to the inhibition of the secretion of TG into circulation. PFOA-induced hepatic accumulation of TG is prevented by the feeding of the FO diet which inhibits TG formation. Among three dietary oils, FO-feeding alone prevented the PFOA-caused accumulation of TG in the liver. The importance of docosahexaenoic acid (22:6(n - 3)) is discussed in relation to the prevention of fatty liver induced by chemicals.

[1]  C. Drevon,et al.  Serum lipids, hepatic glycerolipid metabolism and peroxisomal fatty acid oxidation in rats fed omega-3 and omega-6 fatty acids. , 1992, The Biochemical journal.

[2]  P. Nestel,et al.  Comparative effects of dietary fish oil and carbohydrate on plasma lipids and hepatic activities of phosphatidate phosphohydrolase, diacylglycerol acyltransferase and neutral lipase activities in the rat. , 1987, Biochimica et biophysica acta.

[3]  R. A. Guenthner,et al.  Surface Active Materials from Perfluorocarboxylic and Perfluorosulfonic Acids , 1962 .

[4]  W. J. Dyer,et al.  A rapid method of total lipid extraction and purification. , 1959, Canadian journal of biochemistry and physiology.

[5]  S. Wong,et al.  Eicosapentaenoic acid inhibits the secretion of triacylglycerol and of apoprotein B and the binding of LDL in Hep G2 cells. , 1987, Atherosclerosis.

[6]  W. R. Morrison,et al.  PREPARATION OF FATTY ACID METHYL ESTERS AND DIMETHYLACETALS FROM LIPIDS WITH BORON FLUORIDE--METHANOL. , 1964, Journal of lipid research.

[7]  H. Glauert,et al.  Perfluorodecanoic acid noncompetitively inhibits the peroxisomal enzymes enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase. , 1993, Toxicology and applied pharmacology.

[8]  C. Drevon,et al.  Eicosapentaenoic acid reduces hepatic synthesis and secretion of triacylglycerol by decreasing the activity of acyl-coenzyme A:1,2-diacylglycerol acyltransferase. , 1988, Journal of lipid research.

[9]  J. Groener,et al.  The effect of fasting and refeeding on the composition and synthesis of triacylglycerols, phosphatidylcholines, and phosphatidylethanolamines in rat liver. , 1979, Archives of biochemistry and biophysics.

[10]  M. D. Rosenthal,et al.  Fatty acid metabolism of isolated mammalian cells. , 1987, Progress in lipid research.

[11]  Christine Dreyer,et al.  Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors , 1992, Cell.

[12]  R. Thurman,et al.  Induction of peroxisomes by treatment with perfluorooctanoate does not increase rates of H2O2 production in intact liver. , 1992, Toxicology letters.

[13]  S. Wong,et al.  The adaptive effects of dietary fish and safflower oil on lipid and lipoprotein metabolism in perfused rat liver. , 1984, Biochimica et biophysica acta.

[14]  M. Sugano,et al.  Stimulation of the activities of hepatic fatty acid oxidation enzymes by dietary fat rich in alpha-linolenic acid in rats. , 1996, Journal of lipid research.

[15]  I. Issemann,et al.  Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators , 1990, Nature.

[16]  J. Thorp,et al.  Modification of Metabolism and Distribution of Lipids by Ethyl Chlorophenoxyisobutyrate , 1962, Nature.

[17]  M Tanaka,et al.  The induction of peroxisome proliferation in rat liver by perfluorinated fatty acids, metabolically inert derivatives of fatty acids. , 1985, Journal of biochemistry.

[18]  D. S. Lin,et al.  Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Endo Mamoru,et al.  Identification of shellfish fatty acids and their effects on lipogenic enzymes. , 1980 .

[20]  O. Spydevold,et al.  The mechanism underlying the hypolipemic effect of perfluorooctanoic acid (PFOA), perfluorooctane sulphonic acid (PFOSA) and clofibric acid. , 1992, Biochimica et biophysica acta.

[21]  B. Limoges,et al.  Reduction of hyperlipidemia in the LA/N-corpulent rat by dietary fish oil containing n-3 fatty acids. , 1988, Biochimica et biophysica acta.

[22]  L. Barstad,et al.  DIETARY OMEGA‐3 FATTY ACID DEFICIENCY AND VISUAL LOSS IN INFANT RHESUS MONKEYS , 1985, The Journal of clinical investigation.

[23]  Russell K Yamazaki,et al.  A diet rich in (n-3) fatty acids increases peroxisomal beta-oxidation activity and lowers plasma triacylglycerols without inhibiting glutathione-dependent detoxication activities in the rat liver. , 1987, Biochimica et biophysica acta.

[24]  Reddy Jk,et al.  Carcinogenesis by Hepatic Peroxisome Proliferators: Evaluation of the Risk of Hypolipidemic Drugs and Industrial Plasticizers to Humans , 1983 .

[25]  H. Sprecher,et al.  The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in rat liver is independent of a 4-desaturase. , 1991, The Journal of biological chemistry.

[26]  Y. Kawashima,et al.  Differential effects of altered hormonal state on the induction of acyl-CoA hydrolases and peroxisomal beta-oxidation by clofibric acid. , 1983, Biochimica et biophysica acta.

[27]  M. Wirth,et al.  A possible contribution of decrease in free fatty acids to low serum triglyceride levels after diets supplemented with n-6 and n-3 polyunsaturated fatty acids. , 1990, Atherosclerosis.

[28]  H. Okuyama,et al.  Effect of the dietary alpha-linolenate/linoleate balance on lipid compositions and learning ability of rats. II. Discrimination process, extinction process, and glycolipid compositions. , 1988, Journal of lipid research.

[29]  W. Jones,et al.  The effect of peroxisome proliferators on microsomal, peroxisomal, and mitochondrial enzyme activities in the liver and kidney. , 1987, Drug metabolism reviews.

[30]  Y. Kawashima,et al.  The mechanism for the increased supply of phosphatidylcholine for the proliferation of biological membranes by clofibric acid, a peroxisome proliferator. , 1994, Biochimica et biophysica acta.

[31]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[32]  M E Andersen,et al.  The acute toxicity of perfluorooctanoic and perfluorodecanoic acids in male rats and effects on tissue fatty acids. , 1983, Toxicology and applied pharmacology.