Overexpression of Long-Chain Acyl-CoA Synthetase 5 Increases Fatty Acid Oxidation and Free Radical Formation While Attenuating Insulin Signaling in Primary Human Skeletal Myotubes
| Autor: | Hyo-Bum Kwak, Ronald N. Cortright, P. Darrell Neufer, Julie H. Cox, Tracey L. Woodlief, Robert C. Hickner, Thomas D. Green |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Free Radicals Health Toxicology and Mutagenesis Muscle Fibers Skeletal lcsh:Medicine Mitochondrion Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Coenzyme A Ligases medicine Myocyte Humans Insulin Obesity skeletal muscle Muscle Skeletal Beta oxidation insulin signaling Cells Cultured fatty acid oxidation 030304 developmental biology 2. Zero hunger 0303 health sciences biology Myogenesis Chemistry Superoxide Fatty Acids lcsh:R Public Health Environmental and Occupational Health Skeletal muscle ROS 030229 sport sciences Metabolism Lipid Metabolism 3. Good health Mitochondria Muscle mitochondria Insulin receptor Endocrinology medicine.anatomical_structure ACSL-5 biology.protein Female Oxidation-Reduction Signal Transduction |
| Zdroj: | International Journal of Environmental Research and Public Health Volume 16 Issue 7 International Journal of Environmental Research and Public Health, Vol 16, Iss 7, p 1157 (2019) |
| ISSN: | 1660-4601 |
| DOI: | 10.3390/ijerph16071157 |
| Popis: | In rodent skeletal muscle, acyl-coenzyme A (CoA) synthetase 5 (ACSL-5) is suggested to localize to the mitochondria but its precise function in human skeletal muscle is unknown. The purpose of these studies was to define the role of ACSL-5 in mitochondrial fatty acid metabolism and the potential effects on insulin action in human skeletal muscle cells (HSKMC). Primary myoblasts isolated from vastus lateralis (obese women (body mass index (BMI) = 34.7 ± 3.1 kg/m2)) were transfected with ACSL-5 plasmid DNA or green fluorescent protein (GFP) vector (control), differentiated into myotubes, and harvested (7 days). HSKMC were assayed for complete and incomplete fatty acid oxidation ([1-14C] palmitate) or permeabilized to determine mitochondrial respiratory capacity (basal (non-ADP stimulated state 4), maximal uncoupled (carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP)-linked) respiration, and free radical (superoxide) emitting potential). Protein levels of ACSL-5 were 2-fold higher in ACSL-5 overexpressed HSKMC. Both complete and incomplete fatty acid oxidation increased by 2-fold (p < 0.05). In permeabilized HSKMC, ACSL-5 overexpression significantly increased basal and maximal uncoupled respiration (p < 0.05). Unexpectedly, however, elevated ACSL-5 expression increased mitochondrial superoxide production (+30%), which was associated with a significant reduction (p < 0.05) in insulin-stimulated p-Akt and p-AS160 protein levels. We concluded that ACSL-5 in human skeletal muscle functions to increase mitochondrial fatty acid oxidation, but contrary to conventional wisdom, is associated with increased free radical production and reduced insulin signaling. |
| Databáze: | OpenAIRE |
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