Tags

Type your tag names separated by a space and hit enter

Overexpression of carnitine palmitoyltransferase I in skeletal muscle in vivo increases fatty acid oxidation and reduces triacylglycerol esterification.
Am J Physiol Endocrinol Metab. 2007 Apr; 292(4):E1231-7.AJ

Abstract

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.

Authors+Show Affiliations

Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst. clinton.bruce@baker.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17179390

Citation

Bruce, Clinton R., et al. "Overexpression of Carnitine Palmitoyltransferase I in Skeletal Muscle in Vivo Increases Fatty Acid Oxidation and Reduces Triacylglycerol Esterification." American Journal of Physiology. Endocrinology and Metabolism, vol. 292, no. 4, 2007, pp. E1231-7.
Bruce CR, Brolin C, Turner N, et al. Overexpression of carnitine palmitoyltransferase I in skeletal muscle in vivo increases fatty acid oxidation and reduces triacylglycerol esterification. Am J Physiol Endocrinol Metab. 2007;292(4):E1231-7.
Bruce, C. R., Brolin, C., Turner, N., Cleasby, M. E., van der Leij, F. R., Cooney, G. J., & Kraegen, E. W. (2007). Overexpression of carnitine palmitoyltransferase I in skeletal muscle in vivo increases fatty acid oxidation and reduces triacylglycerol esterification. American Journal of Physiology. Endocrinology and Metabolism, 292(4), E1231-7.
Bruce CR, et al. Overexpression of Carnitine Palmitoyltransferase I in Skeletal Muscle in Vivo Increases Fatty Acid Oxidation and Reduces Triacylglycerol Esterification. Am J Physiol Endocrinol Metab. 2007;292(4):E1231-7. PubMed PMID: 17179390.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of carnitine palmitoyltransferase I in skeletal muscle in vivo increases fatty acid oxidation and reduces triacylglycerol esterification. AU - Bruce,Clinton R, AU - Brolin,Camilla, AU - Turner,Nigel, AU - Cleasby,Mark E, AU - van der Leij,Feike R, AU - Cooney,Gregory J, AU - Kraegen,Edward W, Y1 - 2006/12/19/ PY - 2006/12/21/pubmed PY - 2007/5/22/medline PY - 2006/12/21/entrez SP - E1231 EP - 7 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 292 IS - 4 N2 - 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. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/17179390/Overexpression_of_carnitine_palmitoyltransferase_I_in_skeletal_muscle_in_vivo_increases_fatty_acid_oxidation_and_reduces_triacylglycerol_esterification_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00561.2006?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -