Etomoxir-induced partial CPT-I inhibition in vivo does not alter cardiac long-chain fatty acid uptake and oxidation rates - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Biochemical Journal Année : 2009

Etomoxir-induced partial CPT-I inhibition in vivo does not alter cardiac long-chain fatty acid uptake and oxidation rates

Joost J.F.P. Luiken
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Hanneke E.C. Niessen
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Susan L.M. Coort
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Nicole Hoebers
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Will A. Coumans
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Robert W. Schwenk
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Arend Bonen
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Jan F.C. Glatz
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Résumé

Although carnitine palmitoyltransferase-I (CPT-I) is generally regarded to present a major rate-controlling site in mitochondrial β-oxidation, it is incompletely understood whether CPT-I is rate-limiting in the overall long-chain fatty acid (LCFA) flux in the heart. Another important site of regulation of the LCFA flux in the heart is trans-sarcolemmal LCFA transport facilitated by CD36 and FABPpm. Therefore, we explored to what extent a chronic pharmacological blockade of the LCFA flux at the level of mitochondrial entry of LCFA-CoA would affect sarcolemmal LCFA uptake. Rats were injected daily with saline or etomoxir, a specific CPT-I inhibitor, for 8 days at 20 mg/kg body mass. Etomoxir-treated rats displayed a 44% reduced cardiac CPT-I activity. Sarcolemmal contents of CD36 and FABPpm, as well as the LCFA transport capacity were not altered in hearts of etomoxir-treated versus control rats. Furthermore, rates of LCFA uptake and -oxidation and glucose uptake by cardiac myocytes from etomoxir-treated rats were not different from control rats, neither under basal nor under acutely induced maximal metabolic demands. Finally, hearts from etomoxir-treated rats did not display triacylglycerol accumulation. Therefore, CPT-I appears not to present a major rate-controlling site in total cardiac LCFA flux. Likely, sarcolemmal LCFA entry rather than mitochondrial LCFA-CoA entry is a promising target for normalizing LCFA flux in cardiac metabolic diseases.

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hal-00479121 , version 1 (30-04-2010)

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Joost J.F.P. Luiken, Hanneke E.C. Niessen, Susan L.M. Coort, Nicole Hoebers, Will A. Coumans, et al.. Etomoxir-induced partial CPT-I inhibition in vivo does not alter cardiac long-chain fatty acid uptake and oxidation rates. Biochemical Journal, 2009, 419 (2), pp.447-455. ⟨10.1042/BJ20082159⟩. ⟨hal-00479121⟩

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