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
Author
Kwak, Hyo-Bum; Woodlief, Tracey L.; Green, Thomas D.; Cox, Julie H.; Hickner, Robert C.; Neufer, P. Darrell; Cortright, Ronald N.
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.
Date
2019-03-31
Citation:
APA:
Kwak, Hyo-Bum, & Woodlief, Tracey L., & Green, Thomas D., & Cox, Julie H., & Hickner, Robert C., & Neufer, P. Darrell, & Cortright, Ronald N.. (March 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.
,
(),
-
. Retrieved from
http://hdl.handle.net/10342/8252
MLA:
Kwak, Hyo-Bum, and Woodlief, Tracey L., and Green, Thomas D., and Cox, Julie H., and Hickner, Robert C., and Neufer, P. Darrell, and Cortright, Ronald N..
"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". .
. (),
March 2019.
September 30, 2023.
http://hdl.handle.net/10342/8252.
Chicago:
Kwak, Hyo-Bum and Woodlief, Tracey L. and Green, Thomas D. and Cox, Julie H. and Hickner, Robert C. and Neufer, P. Darrell and Cortright, Ronald N.,
"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," , no.
(March 2019),
http://hdl.handle.net/10342/8252 (accessed
September 30, 2023).
AMA:
Kwak, Hyo-Bum, Woodlief, Tracey L., Green, Thomas D., Cox, Julie H., Hickner, Robert C., Neufer, P. Darrell, Cortright, Ronald N..
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. .
March 2019;
():
.
http://hdl.handle.net/10342/8252. Accessed
September 30, 2023.
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