Lipids

, Volume 34, Issue 9, pp 951–963

Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference

Authors

    • Department of Clinical BiochemistryUniversity of Bergen, Haukeland Hospital
  • Arild C. Rustan
    • Department of Pharmacology, School of PharmacyUniversity of Oslo
  • Hege Vaagenes
    • Department of Clinical BiochemistryUniversity of Bergen, Haukeland Hospital
  • Kjetil Berge
    • Department of Clinical BiochemistryUniversity of Bergen, Haukeland Hospital
  • Endre Dyrøy
    • Department of Clinical BiochemistryUniversity of Bergen, Haukeland Hospital
  • Rolf K. Berge
    • Department of Clinical BiochemistryUniversity of Bergen, Haukeland Hospital
Article

DOI: 10.1007/s11745-999-0445-x

Cite this article as:
Madsen, L., Rustan, A.C., Vaagenes, H. et al. Lipids (1999) 34: 951. doi:10.1007/s11745-999-0445-x

Abstract

Decreased triacylglycerol synthesis within hepatocytes due to decreased diacylglycerol acyltransferase (DGAT) activity has been suggested to be an important mechanism by which diets rich in fish oil lower plasma triacylglycerol levels. New findings suggest that eicosapentaenoic acid (EPA), and not docosahexaenoic acid (DHA), lowers plasma triacylglycerol by increased mitochondrial fatty acid oxidation and decreased availability of fatty acids for triacylglycerol synthesis. To contribute to the understanding of the triacylglycerol-lowering mechanism of fish oil, the different metabolic properties of EPA and DHA were studied in rat liver parenchymal cells and isolated rat liver organelles. EPA-CoA was a poorer substrate than DHA-CoA for DGAT in isolated rat liver microsomes, and in the presence of EPA, a markedly lower value for the triacyl[3H]glycerol/diacyl[3H]glycerol ratio was observed. The distribution of [1-14C]palmitic acid was shifted from incorporation into secreted glycerolipids toward oxidation in the presence of EPA (but not DHA) in rat liver parenchymal cells. [1-14C]EPA was oxidized to a much greater extent than [1-14C]DHA in rat liver parenchymal cells, isolated peroxisomes, and especially in purified mitochondria. As the oxidation of EPA was more effective and sensitive to the CPT-I inhibitor, etomoxir, when measured in a combination of both mitochondria and peroxisomes, we hypothesized that both are involved in EPA oxidation, whereas DHA mainly is oxidized in peroxisomes. In rats, EPA treatment lowered plasma triacylglycerol and increased hepatic mitochondrial fatty acid oxidation and carnitine palmitoyltransferase (CPT)-I activity in both the presence and absence of malonyl-CoA. Whereas only EPA treatment increased the mRNA levels of CPT-I, DHA treatment increased the mRNA levels of peroxisomal fatty acyl-CoA oxidase and fatty acid binding protein more effectively than EPA treatment. In conclusion, EPA and DHA affect cellular organelles in relation to their substrate preference. The present study strongly supports the hypothesis that EPA, and not DHA, lowers plasma triacylglycerol by increased mitochondrial fatty acid oxidation.

Abbreviations

BSA

bovine serum albumin

CMC

carboxymethyl cellulose

CPT

carnitine palmitoyltransferase

DGAT

diacylglycerol acyltransferase

DHA

docosahexaenoic acid

DMEM

Dulbecco’s modified Eagle’s medium

EPA

eicosapentaenoic acid

FABP

fatty acid binding protein

FAO

fatty acyl-CoA oxidase

PPAR

peroxisome proliferator activated receptor

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Copyright information

© AOCS Press 1999