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The role of toll‐like receptor 4 in mitochondrial function and reactive oxygen species (ROS) production in skeletal muscle
Author(s) -
Wu Yaru,
Frisard Madlyn,
Shabrokh Elike,
Voelker Kevin,
McMilian Ryan P,
Hulver Matthew W
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.1051.22
Subject(s) - skeletal muscle , myogenesis , reactive oxygen species , mitochondrial ros , mitochondrion , medicine , endocrinology , myocyte , chemistry , tlr4 , oxidative phosphorylation , gastrocnemius muscle , biology , microbiology and biotechnology , biochemistry , receptor
Toll‐like receptor 4 (TLR4) is elevated in skeletal muscle of obese humans, and data from our lab showed that activation of TLR4 in skeletal muscle with lipopplysaccharide (LPS) results in decreased fatty acid oxidation. The purpose of this study was to determine if TLR4 activation in skeletal muscle alters mitochondrial function and increases the production of ROS. C2C12 and human primary myotubes, and mitochondria isolated from rodent gastrocnemius muscle studied. TLR4 activation (LPS 50pg/ml for 2h) resulted in a significant reduction in maximal oxidative respiration in both C2C12 and human primary myotubes, which was observed in concert with an increase in production of ROS, and alterations in mitochondrial gene expression and protein content. These effects were blocked in the presence of the antioxidant, N‐acetyl cysteine (NAC). Moreover, mitochondria isolated from skeletal muscle of mice 4 hours following an intraperitoneal injection of LPS (1mg/kg) displayed reduced respiratory control, ADP‐stimulated respiration, and maximal respiration. These findings suggest that TLR4 activation causes mitochondrial dysfunction in skeletal muscle, which is partially dependent on the production of ROS.