Primary defects in lipid handling and resistance to exercise in myotubes from obese donors with and without type 2 diabetes

Several studies have shown that human primary myotubes retain the metabolic characteristic of their donors in vitro. Others and we have demonstrated a reduced lipid turnover and fat oxidation rate in myotubes derived from obese donors without and with type 2 diabetes (T2D). Because exercise is known to increase fat oxidative capacity in skeletal muscle, we investigated if in vitro exercise could restore primary defects in lipid handling in myotubes of obese without and with T2D compared to lean non-diabetic donors. Primary myotubes cultures were derived from biopsies of lean, obese and T2D subjects. One single bout of long-duration exercise was mimicked in vitro by electrical pulse stimulation (EPS) for 24 h. Lipid handling was measured using radiolabeled palmitate, Metabolic gene expression by real-time qPCR, and proteins by western blot. We first show that myotubes from obese and T2D donors had increased uptake and incomplete oxidation of palmitate. This was associated with reduced mitochondrial respiratory chain complex II, III and IV protein expression in myotubes from obese and T2D subjects. EPS stimulated palmitate oxidation in lean donors, while myotubes from obese and T2D donors were refractory to this effect. Interestingly, EPS increased total palmitate uptake in myotubes from lean donors while myotubes from T2D donors had a reduced rate of palmitate uptake into complex lipids and triacylglycerols. Novelty: • Myotubes from obese and T2D donors are characterized by primary defects in palmitic acid handling. • Both obese and T2D myotubes are partially refractory to the beneficial effect of exercise on lipid handling.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author