Quercetin is a potent anti-inflammatory flavonoid, but its capacity to modulate insulin sensitivity in obese insulin resistant conditions is unknown. This study investigated the effect of quercetin treatment upon insulin sensitivity of ob/ob mice and its potential molecular mechanisms. Obese ob/ob mice were treated with quercetin for 10 weeks, and L6 myotubes were treated with either palmitate or tumor necrosis factor-á (TNFá) plus quercetin. Cells and muscles were processed for analysis of glucose transporter 4 (GLUT4), TNFá and inducible nitric oxide synthase (iNOS) expression, and c-Jun N-terminal kinase (JNK) and inhibitor of nuclear factor-êB (NF-êB) kinase (IêK) phosphorylation. Myotubes were assayed for glucose uptake and NF-êB translocation. Chromatin immunoprecipitation assessed NF-êB binding to GLUT4 promoter. Quercetin treatment improved whole body insulin sensitivity by increasing GLUT4 expression and decreasing JNK phosphorylation, and TNFá and iNOS expression in skeletal muscle. Quercetin suppressed palmitate-induced upregulation of TNFá and iNOS and restored normal levels of GLUT4 in myotubes. In parallel, quercetin suppressed TNFá-induced reduction of glucose uptake in myotubes. Nuclear accumulation of NF-êB in myotubes and binding of NF-êB to GLUT4 promoter in muscles of ob/ob mice were also reduced by quercetin. We demonstrated that quercetin decreased the inflammatory status in skeletal muscle of obese mice and in L6 myotubes. This effect was followed by increased muscle GLUT4, with parallel improvement of insulin sensitivity. These results point out quercetin as a putative strategy to manage inflammatory-related insulin resistance.
Animals Antioxidants