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

Hyo Bum Kwak, Tracey L. Woodlief, Thomas D. Green, Julie H. Cox, Robert C. Hickner, P. Darrell Neufer, Ronald N. Cortright

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
11 Downloads (Pure)

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.

Original languageEnglish
Article number1157
Pages (from-to)1-15
Number of pages15
JournalInternational Journal of Environmental Research and Public Health
Volume16
Issue number7
DOIs
Publication statusPublished - 1 Apr 2019
Externally publishedYes

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this