Resveratrol Alleviates Lipid‐Induced Insulin Resistance in Lean, But Not Severely Obese, Myotubes

Abstract

Excessive lipid exposure is associated with various disease states, including severe obesity (BMI > 40 kg/m2), and can lead to insulin resistance. This whole‐body defect in insulin action following chronic lipid exposure is also observed at the cellular level, as myotubes from severely obese humans have a blunted response to insulin. Resveratrol, a natural polyphenolic compound, has been proposed to improve these defects in insulin signaling; however, it is uncertain whether resveratrol can recover the acute and imprinted defects associated with lipid exposure. To examine this, human skeletal muscle cells were isolated from muscle biopsies obtained from lean (BMI = 21.21 ± 0.50 kg/m2) and severely obese (BMI = 53.41±1.61 kg/m2) individuals, and differentiated into myotubes. Myotubes were exposed to palmitate (0.45 mM) for 16 hours to induce insulin resistance in the presence or absence of resveratrol (0.2 μM). Myotubes were then treated with insulin (100 nM) and harvested for examination of insulin signaling. Palmitate suppressed insulin‐induced phosphorylation of AKT (Ser473) by 38% in lean myotubes, which was rescued with resveratrol treatment. Conversely, in comparison to lean controls, resveratrol treatment did not improve insulin action in obese myotubes. These data show that resveratrol treatment can enhance insulin signaling following acute lipid exposure; however, it cannot improve the inherent defects associated with severe obesity.