Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation
The 3-thia fatty acids, tetradecylthioacetic acid and 3,10-dithiadicarboxylic acid are mitochondrion and peroxisome proliferators. Administration of these promotes an increased transport of endogenous fatty acids to these organelles and a higher capacity of β-oxidation. Administration of 3-thia fatt...
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doaj-47dfa39277284c0fbdbeccd478e8c8402021-04-26T05:46:24ZengElsevierJournal of Lipid Research0022-22751998-03-01393583593Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferationLise Madsen0Livar Frøyland1Endre Dyrøy2Kari Helland3Rolf K. Berge4To whom correspondence should be addressed.; Department of Clinical Biochemistry, University of Bergen, Haukeland Hospital, N-5021 Bergen, NorwayDepartment of Clinical Biochemistry, University of Bergen, Haukeland Hospital, N-5021 Bergen, NorwayDepartment of Clinical Biochemistry, University of Bergen, Haukeland Hospital, N-5021 Bergen, NorwayDepartment of Clinical Biochemistry, University of Bergen, Haukeland Hospital, N-5021 Bergen, NorwayDepartment of Clinical Biochemistry, University of Bergen, Haukeland Hospital, N-5021 Bergen, NorwayThe 3-thia fatty acids, tetradecylthioacetic acid and 3,10-dithiadicarboxylic acid are mitochondrion and peroxisome proliferators. Administration of these promotes an increased transport of endogenous fatty acids to these organelles and a higher capacity of β-oxidation. Administration of 3-thia fatty acids to rats resulted in a significant decrease of the hepatic level of docosahexaenoic acid (DHA) (17–24%) and especially eicosapentaenoic acid (EPA) (40–80%) accompanied by increased gene expression of mitochondrial 2,4-dienoylCoA reductase and enoyl-CoA isomerase. The mitochondrial oxidation of EPA was increased more than 4-fold after administration of 3-thia fatty acids. EPA-CoA was a good substrate for mitochondrial carnitine acyltransferase-I and treatment with 3-thia fatty acids increased the activity 1.7-fold. DHA was a poor substrate for both mitochondrial and peroxisomal β-oxidation. DHA-CoA was a very poor substrate for mitochondrial carnitine acyltransferase-I and -II, and the activity did not increase after treatment. However, the peroxisomal DHA-CoA oxidase increased 10-fold after 3-thia fatty acid treatment, whereas the peroxisomal EPA-CoA oxidase increased only 5-fold. In isolated hepatocytes, 16% of total metabolized EPA was oxidized and 76% was incorporated into glycerolipids, whereas DHA was oxidized very little. We conclude that under conditions of increased mitochondrial and peroxisomal proliferation by 3-thia fatty acids, a relatively higher oxidation rate of polyunsaturated n–3 fatty acids might result in a decreased hepatic level of EPA and DHA. Under these conditions DHA seems to be oxidized by the peroxisomes, whereas EPA, which can be oxidized in both organelles, is mainly oxidized by mitochondria.—Madsen, L., L. Frøyland, E. Dyrøy, K. Helland, and R. K. Berge. Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation. J. Lipid Res. 39: 583–593.http://www.sciencedirect.com/science/article/pii/S002222752033296X3-thia fatty acidsfatty acyl-CoA oxidasecarnitine acyltransferaseliverEPADHA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lise Madsen Livar Frøyland Endre Dyrøy Kari Helland Rolf K. Berge |
spellingShingle |
Lise Madsen Livar Frøyland Endre Dyrøy Kari Helland Rolf K. Berge Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation Journal of Lipid Research 3-thia fatty acids fatty acyl-CoA oxidase carnitine acyltransferase liver EPA DHA |
author_facet |
Lise Madsen Livar Frøyland Endre Dyrøy Kari Helland Rolf K. Berge |
author_sort |
Lise Madsen |
title |
Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation |
title_short |
Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation |
title_full |
Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation |
title_fullStr |
Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation |
title_full_unstemmed |
Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation |
title_sort |
docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
1998-03-01 |
description |
The 3-thia fatty acids, tetradecylthioacetic acid and 3,10-dithiadicarboxylic acid are mitochondrion and peroxisome proliferators. Administration of these promotes an increased transport of endogenous fatty acids to these organelles and a higher capacity of β-oxidation. Administration of 3-thia fatty acids to rats resulted in a significant decrease of the hepatic level of docosahexaenoic acid (DHA) (17–24%) and especially eicosapentaenoic acid (EPA) (40–80%) accompanied by increased gene expression of mitochondrial 2,4-dienoylCoA reductase and enoyl-CoA isomerase. The mitochondrial oxidation of EPA was increased more than 4-fold after administration of 3-thia fatty acids. EPA-CoA was a good substrate for mitochondrial carnitine acyltransferase-I and treatment with 3-thia fatty acids increased the activity 1.7-fold. DHA was a poor substrate for both mitochondrial and peroxisomal β-oxidation. DHA-CoA was a very poor substrate for mitochondrial carnitine acyltransferase-I and -II, and the activity did not increase after treatment. However, the peroxisomal DHA-CoA oxidase increased 10-fold after 3-thia fatty acid treatment, whereas the peroxisomal EPA-CoA oxidase increased only 5-fold. In isolated hepatocytes, 16% of total metabolized EPA was oxidized and 76% was incorporated into glycerolipids, whereas DHA was oxidized very little. We conclude that under conditions of increased mitochondrial and peroxisomal proliferation by 3-thia fatty acids, a relatively higher oxidation rate of polyunsaturated n–3 fatty acids might result in a decreased hepatic level of EPA and DHA. Under these conditions DHA seems to be oxidized by the peroxisomes, whereas EPA, which can be oxidized in both organelles, is mainly oxidized by mitochondria.—Madsen, L., L. Frøyland, E. Dyrøy, K. Helland, and R. K. Berge. Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation. J. Lipid Res. 39: 583–593. |
topic |
3-thia fatty acids fatty acyl-CoA oxidase carnitine acyltransferase liver EPA DHA |
url |
http://www.sciencedirect.com/science/article/pii/S002222752033296X |
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