Overexpression of carnitine palmitoyltransferase I in skeletal muscle in vivo increases fatty acid oxidation and reduces triacylglycerol esterification
| Autor: | Nigel Turner, Clinton R. Bruce, Feike R van der Leij, Gregory J. Cooney, Edward W. Kraegen, Mark E. Cleasby, Camilla Brolin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
LIVER endocrine system diseases Physiology Endocrinology Diabetes and Metabolism Palmitates Mitochondrion INTERMYOFIBRILLAR chemistry.chemical_compound heterocyclic compounds Inner mitochondrial membrane Beta oxidation chemistry.chemical_classification INSULIN-RESISTANCE Palmitoyl Coenzyme A Fatty Acids Hindlimb mitochondria Electroporation medicine.anatomical_structure Biochemistry MALONYL-COA Carnitine palmitoyltransferase I substrate metabolism Oxidation-Reduction hormones hormone substitutes and hormone antagonists medicine.medical_specialty TISSUES In Vitro Techniques Biology muscle lipids METABOLISM Transfection GENE-TRANSFER Physiology (medical) Internal medicine medicine Animals Humans Rats Wistar Muscle Skeletal neoplasms Triglycerides Carnitine O-Palmitoyltransferase Esterification Fatty acid Skeletal muscle Metabolism Lipid Metabolism digestive system diseases Mitochondria Muscle Rats Malonyl-CoA Endocrinology chemistry RAT MEMBRANE Biomarkers |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism, 292(4), E1231-E1237. AMER PHYSIOLOGICAL SOC |
| ISSN: | 0193-1849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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