Differential carnitine/acylcarnitine translocase expression defines distinct metabolic signatures in skeletal muscle cells

Gianfranco Peluso, Orsolina Petillo, Sabrina Margarucci, Pasquale Grippo, M. A B Melone, Franca Tuccillo, Menotti Calvani

Research output: Contribution to journalArticle

Abstract

Import of acylcarnitine into mitochondrial matrix through carnitine/acylcarnitine-translocase (CACT) is fundamental for lipid catabolism. To probe the effect of CACT down-expression on lipid metabolism in muscle, human myocytes were stably transfected with CACT-antisense construct. In presence of low concentration of palmitate, transfected cells showed decreased palmitate oxidation and acetyl-carnitine content, increased palmitoyl-carnitine level, and reduced insulin-dependent decrease of fatty acylcarnitine-to-fatty acyl-CoA ratio. The augmented palmitoyl-carnitine synthesis, also in the presence of insulin, could be related to an altered regulation of carnitine-palmitoyl- transferase 1 (CPT 1) by malonyl-CoA, whose synthesis is dependent by the availability of cytosolic acetyl-groups. Indeed, all the described effects were completely overcome by CACT neo-expression by recombinant adenovirus vector or by addition of acetyl-carnitine to cultures. Acetyl-carnitine effect was related to an increase of malonyl-CoA and was abolished by down-expression, via antisense RNA strategy, of acetyl-CoA carboxylase-β, the mitochondrial membrane enzyme involved in the direct CPT 1 inhibition via malonyl-CoA synthesis. Thus, in our experimental model the modulation of CACT expression has consequences for CPT 1 activity, while the biologic effects of acetyl-carnitine are not associated with a generic supply of energy compounds but to the anaplerotic property of the molecule.

Original languageEnglish
Pages (from-to)439-446
Number of pages8
JournalJournal of Cellular Physiology
Volume203
Issue number2
DOIs
Publication statusPublished - May 2005

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

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