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Overexpression of long chain acyl‐CoA synthetase 1 increases fatty acid oxidation in primary human skeletal myotubes
Author(s) -
Kwak HyoBum,
Woodlief Tracey L.,
Green Thomas D.,
Cox Julie H.,
Hickner Robert C.,
Neufer P. Darrell,
Cortright Ronald N.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1104.9
Subject(s) - skeletal muscle , beta oxidation , biochemistry , fatty acid , myogenesis , chemistry , glycolysis , lipid oxidation , medicine , endocrinology , biology , metabolism , antioxidant
In liver, long chain acyl‐CoA synthetase (ACSL) activates fatty acids and plays a key role in their partitioning toward oxidation or storage, but little data exist from human skeletal muscle. The purpose of this study was to determine the effects of ACSL‐1 overexpression (ACSL‐1 OEX ) on fatty acid oxidation (FAO; CO 2 production and O 2 consumption) and total lipid synthesis in human skeletal muscle cells (HSKMC). Primary myoblasts isolated from vastus lateralis (N=5) were transfected with ACSL‐1 plasmid DNA, differentiated into myotubes and harvested (7 d) to measure FAO ([1‐ 14 C] palmitate), or permeabilized for determination of mitochondrial respiration. The protein levels of ACSL‐1 were 38% higher in ACSL‐1 OEX HSKMC. Both complete (CO 2 ) and incomplete (ASM) FAO increased by approximately 2‐fold (P < 0.05). In permeabilized HSKMC supported by fatty acids, both maximal ADP‐stimulated (state 3) and maximal uncoupled (FCCP‐linked) oxygen consumption were significantly increased in ACSL‐1 OEX (P<0.05), implying greater fatty acid catabolic flux capacity. However, ACSL‐1 overexpression did not affect total lipid synthesis. These data demonstrate that ACSL‐1 overexpression in HSKMC increases FAO as well as maximal stimulated (ADP & FCCP) respiration without affecting total lipid storage, suggesting that activation of fatty acids is at least partially rate limiting for fatty acid oxidation. Supported by NIH DK075880 (RNC) and DK073488 (PDN).