TY - JOUR
T1 - Key glycolytic metabolites in paralyzed skeletal muscle are altered seven days after spinal cord injury in Mice
AU - Graham, Zachary A.
AU - Siedlik, Jacob A.
AU - Harlow, Lauren
AU - Sahbani, Karim
AU - Bauman, William A.
AU - Tawfeek, Hesham A.
AU - Cardozo, Christopher P.
N1 - Funding Information:
Research support was provided by the Department of Veterans Affairs Rehabilitation Research & Development Service’s National Center for the Medical Consequences of Spinal Cord Injury (B2020C). The services for metabolomics were provided by West Coast Metabolomics (NIH grant 1U24DK097154; PI: Oliver Fiehn).
PY - 2019/9/15
Y1 - 2019/9/15
N2 - 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.
AB - 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.
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U2 - 10.1089/neu.2018.6144
DO - 10.1089/neu.2018.6144
M3 - Article
C2 - 30869558
AN - SCOPUS:85071785595
VL - 36
SP - 2722
EP - 2731
JO - Central Nervous System Trauma
JF - Central Nervous System Trauma
SN - 0897-7151
IS - 18
ER -