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This Article Full Text Full Text (PDF) All Versions of this Article: 292/4/E1231    most recent 00561.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Bruce, C. R. Articles by Kraegen, E. W. Search for Related Content PubMed PubMed Citation Articles by Bruce, C. R. Articles by Kraegen, E. W.

Overexpression of carnitine palmitoyltransferase I in skeletal muscle in vivo increases fatty acid oxidation and reduces triacylglycerol esterification

¹Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst; ²School of Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia; ³Pediatrics Department, University of Groningen, Groningen; ⁴Unit Life Sciences, Van Hall University of Applied Sciences, Leeuwarden, The Netherlands; and ⁵St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, New South Wales, Australia

Submitted 15 October 2006 ; accepted in final form 14 December 2006

A key regulatory point in the control of fatty acid (FA) oxidation is thought to be transport of FAs across the mitochondrial membrane by carnitine palmitoyltransferase I (CPT I). To investigate the role of CPT I in FA metabolism, we used in vivo electrotransfer (IVE) to locally overexpress CPT I in muscle of rodents. A vector expressing the human muscle isoform of CPT I was electrotransferred into the right lateral muscles of the distal hindlimb [tibialis cranialis (TC) and extensor digitorum longus (EDL)] of rats, and a control vector expressing GFP was electrotransferred into the left muscles. Initial studies showed that CPT I protein expression peaked 7 days after IVE (+104%, P < 0.01). This was associated with an increase in maximal CPT I activity (+30%, P < 0.001) and a similar increase in palmitoyl-CoA oxidation (+24%; P < 0.001) in isolated mitochondria from the TC. Importantly, oxidation of the medium-chain FA octanoyl-CoA and CPT I sensitivity to inhibition by malonyl-CoA were not altered by CPT I overexpression. FA oxidation in isolated EDL muscle strips was increased with CPT I overexpression (+28%, P < 0.01), whereas FA incorporation into the muscle triacylglycerol (TAG) pool was reduced (–17%, P < 0.01). As a result, intramyocellular TAG content was decreased with CPT I overexpression in both the TC (–25%, P < 0.05) and the EDL (–45%, P < 0.05). These studies demonstrate that acute overexpression of CPT I in muscle leads to a repartitioning of FAs away from esterification and toward oxidation and highlight the importance of CPT I in regulating muscle FA metabolism.

mitochondria; muscle lipids; substrate metabolism