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3-thia fatty acid treatment, in contrast to eicosapentaenoic acid and starvation, induces gene expression of carnitine palmitoyltransferase-II in rat liver

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Lipids

Abstract

The aim of the present study was to investigate the hepatic regulation and β-oxidation of long-chain fatty acids in peroxisomes and mitochondria, after 3-thia- tetradecylthioacetic acid (C14-S-acetic acid) treatment. When palmitoyl-CoA and palmitoyl-l-carnitine were used as substrates, hepatic formation of acid-soluble products was significantly increased in C14-S-acetic acid treated rats. Administration of C14-S-acetic acid resulted in increased enzyme activity and mRNA levels of hepatic mitochondrial carnitine palmitoyltransferase (CPT)-II. CPT-II activity correlated with both palmitoyl-CoA and palmitoyl-l-carnitine oxidation in rats treated with different chain-length 3-thia fatty acids. CPT-I activity and mRNA levels were, however, marginally affected. The hepatic CPT-II activity was mainly localized in the mitochondrial fraction, whereas the CPT-I activity was enriched in the mitochondrial, peroxisomal, and microsomal fractions. In C14-S-acetic acid-treated rats, the specific activity of peroxisomal and microsomal CPT-I increased, whereas the mitochondrial activity tended to decrease. C14-S-Acetyl-CoA inhibited CPT-I activity in vitro. The sensitivity of CPT-I to malonyl-CoA was unchanged, and the hepatic malonyl-CoA concentration increased after C14-S-acetic acid treatment. The mRNA levels of acetyl-CoA carboxylase increased. In hepatocytes cultured from palmitic acid- and C14-S-acetic acid-treated rats, the CPT-I inhibitor etomoxir inhibited the formation of acid-soluble products 91 and 21%, respectively. In contrast to 3-thia fatty acid treatment, eicosapentaenoic acid treatment and starvation increased the mitochondrial CPT-I activity and reduced its malonyl-CoA sensitivity. Palmitoyl-l-carnitine oxidation and CPT-II activity were, however, unchanged after either EPA treatment or starvation. The results from this study open the possibility that the rate control of mitochondrial β-oxidation under mitochondrion and peroxisome proliferation is distributed between an enzyme or enzymes of the pathway beyond the CPT-I site after 3-thia fatty acid treatment. It is suggested that fatty acids are partly oxidized in the peroxisomes before entering the mitochondria as acylcarnitines for further oxidation.

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Abbreviations

C14-S-Acetic acid:

tetradecylthioacetic acid

BSA:

bovine serum albumin

CMC:

carboxymethyl cellulose

CPT:

carnitine palmitoyl-transferase

EPA:

cicosapentaenoic acid

PPAR:

peroxisome proliferator activated receptor, Enzymes: carnitine palmitoyltransferase (EC 23.1.21)

acetyl-CoA:

carboxylase (EC 6.4.1.2)

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Haukeland Hospital, University of Bergen, N-5021, Bergen, Norway

    Lise Madsen & Rolf K. Berge

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  1. Lise Madsen
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  2. Rolf K. Berge
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Correspondence to Lise Madsen.

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Madsen, L., Berge, R.K. 3-thia fatty acid treatment, in contrast to eicosapentaenoic acid and starvation, induces gene expression of carnitine palmitoyltransferase-II in rat liver. Lipids 34, 447–456 (1999). https://doi.org/10.1007/s11745-999-0384-6

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  • DOI: https://doi.org/10.1007/s11745-999-0384-6

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