Increased glucose utilization and decreased fatty acid metabolism in myotubes from Glmp(gt/gt) mice

Arch Physiol Biochem. 2016;122(1):36-45. doi: 10.3109/13813455.2015.1120752. Epub 2016 Jan 27.

Abstract

Glycosylated lysosomal membrane protein (GLMP) has been reported to enhance the expression from a peroxisome proliferator-activated receptor alpha (PPARα) responsive promoter, but also to be an integral lysosomal membrane protein. Using myotubes established from wild-type and Glmp(gt/gt) mice, the importance of GLMP in skeletal muscle was examined. Glmp(gt/gt) myotubes expressed a more glycolytic phenotype than wild-type myotubes. Myotubes from Glmp(gt/gt) mice metabolized glucose faster and had a larger pool of intracellular glycogen, while oleic acid uptake, storage and oxidation were significantly reduced. Gene expression analyses indicated lower expression of three PPAR-isoforms, a co-regulator of PPAR (PGC1α) and several genes important for lipid metabolism in Glmp(gt/gt) myotubes. However, ablation of GLMP did not seem to substantially impair the response to PPAR agonists. In conclusion, myotubes established from Glmp(gt/gt) mice were more glycolytic than myotubes from wild-type animals, in spite of no differences in muscle fiber types in vivo.

Keywords: Cultured myotubes; Glycosylated lysosomal membrane protein; energy metabolism; peroxisome proliferator-activated receptor; skeletal muscle.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Fatty Acids / metabolism*
  • Gene Deletion*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Glucose / metabolism*
  • Male
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mice
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • Oleic Acid / metabolism
  • Oxidation-Reduction / drug effects
  • Peroxisome Proliferator-Activated Receptors / agonists
  • Peroxisome Proliferator-Activated Receptors / metabolism

Substances

  • Fatty Acids
  • Membrane Proteins
  • NCU-G1 protein, mouse
  • Peroxisome Proliferator-Activated Receptors
  • Oleic Acid
  • Glucose