Kwak 2019 Int J Environ Res Public Health

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Kwak HB, Woodlief TL, Green TD, Cox JH, Hickner RC, Neufer PD, Cortright RN (2019) 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. Int J Environ Res Public Health 16:E1157.

» PMID: 30935113 Open Access

Kwak HB, Woodlief TL, Green TD, Cox JH, Hickner RC, Neufer PD, Cortright RN (2019) Int J Environ Res Public Health

Abstract: 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.

Keywords: ACSL-5, ROS, Fatty acid oxidation, Insulin signaling, Mitochondria, Skeletal muscle Bioblast editor: Plangger M O2k-Network Lab: KR Incheon Kwak HB, US NC Greenville Neufer PD


Labels: MiParea: Respiration 

Stress:Oxidative stress;RONS  Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized cells 


Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, NS  HRR: Oxygraph-2k 

Labels, 2019-04