Key glycolytic metabolites in paralyzed skeletal muscle are altered seven days after spinal cord injury in Mice

Academic Article

Abstract

  • © Copyright 2019, Mary Ann Liebert, Inc., publishers 2019. Spinal cord injury (SCI) results in rapid muscle atrophy and an oxidative-to-glycolytic fiber-type shift. Those with chronic SCI are more at risk for developing insulin resistance and reductions in glucose clearance than able-bodied individuals, but how glucose metabolism is affected after SCI is not well known. An untargeted metabolomics approach was utilized to investigate changes in whole-muscle metabolites at an acute (7-day) and subacute (28-day) time frame after a complete T9 spinal cord transection in 20-week-old female C57BL/6 mice. Two hundred one metabolites were detected in all samples, and 83 had BinBase IDs. A principal components analysis showed the 7-day group as a unique cluster. Further, 36 metabolites were altered after 7- and/or 28-day post-SCI (p values <0.05), with 12 passing further false discovery rate exclusion criteria; of those 12 metabolites, three important glycolytic molecules - glucose and downstream metabolites pyruvic acid and lactic acid - were reduced at 7 days compared to those values in sham and/or 28-day animals. These changes were associated with altered expression of proteins associated with glycolysis, as well as monocarboxylate transporter 4 gene expression. Taken together, our data suggest an acute disruption of skeletal muscle glucose uptake at 7 days post-SCI, which leads to reduced pyruvate and lactate levels. These levels recover by 28 days post-SCI, but a reduction in pyruvate dehydrogenase protein expression at 28 days post-SCI implies disruption in downstream oxidation of glucose.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Graham ZA; Siedlik JA; Harlow L; Sahbani K; Bauman WA; Tawfeek HA; Cardozo CP
  • Start Page

  • 2722
  • End Page

  • 2731
  • Volume

  • 36
  • Issue

  • 18