Utilization of lactic acid in human myotubes and interplay with glucose and fatty acid metabolism

Abstract

Once assumed only to be a waste product of anaerobe glycolytic activity, lactate is now recognized as an energy source in skeletal muscles. While lactate metabolism has been extensively studied in vivo, underlying cellular processes are poorly described. This study aimed to examine lactate metabolism in cultured human myotubes and to investigate effects of lactate exposure on metabolism of oleic acid and glucose. Lactic acid, fatty acid and glucose metabolism were studied in myotubes using [14C(U)]lactic acid, [14C]oleic acid and [14C(U)]glucose, respectively. Myotubes expressed both the MCT1, MCT2, MCT3 and MCT4 lactate transporters, and lactic acid was found to be a substrate for both glycogen synthesis and lipid storage. Pyruvate and palmitic acid inhibited lactic acid oxidation, whilst glucose and α-cyano-4-hydroxycinnamic acid inhibited lactic acid uptake. Acute addition of lactic acid inhibited glucose and oleic acid oxidation, whereas oleic acid uptake was increased. Pretreatment with lactic acid for 24 h did not affect glucose or oleic acid metabolism. By replacing glucose with lactic acid during the whole culturing period, glucose uptake and oxidation were increased by 2.8-fold and 3-fold, respectively, and oleic acid oxidation was increased 1.4-fold. Thus, lactic acid has an important role in energy metabolism of human myotubes.