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

Zachary A. Graham, Jacob A. Siedlik, Lauren Harlow, Karim Sahbani, William A. Bauman, Hesham A. Tawfeek, Christopher P. Cardozo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2722-2731
Number of pages10
JournalJournal of Neurotrauma
Volume36
Issue number18
DOIs
StatePublished - Sep 15 2019

Fingerprint

Spinal Cord Injuries
Skeletal Muscle
Glucose
Pyruvic Acid
Lactic Acid
Metabolomics
Muscular Atrophy
Glycolysis
Principal Component Analysis
Inbred C57BL Mouse
Insulin Resistance
Oxidoreductases
Proteins
Gene Expression
Muscles

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Key glycolytic metabolites in paralyzed skeletal muscle are altered seven days after spinal cord injury in Mice. / Graham, Zachary A.; Siedlik, Jacob A.; Harlow, Lauren; Sahbani, Karim; Bauman, William A.; Tawfeek, Hesham A.; Cardozo, Christopher P.

In: Journal of Neurotrauma, Vol. 36, No. 18, 15.09.2019, p. 2722-2731.

Research output: Contribution to journalArticle

Graham, Zachary A. ; Siedlik, Jacob A. ; Harlow, Lauren ; Sahbani, Karim ; Bauman, William A. ; Tawfeek, Hesham A. ; Cardozo, Christopher P. / Key glycolytic metabolites in paralyzed skeletal muscle are altered seven days after spinal cord injury in Mice. In: Journal of Neurotrauma. 2019 ; Vol. 36, No. 18. pp. 2722-2731.
@article{16fe3994ee544992a561b361c90bef83,
title = "Key glycolytic metabolites in paralyzed skeletal muscle are altered seven days after spinal cord injury in Mice",
abstract = "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.",
author = "Graham, {Zachary A.} and Siedlik, {Jacob A.} and Lauren Harlow and Karim Sahbani and Bauman, {William A.} and Tawfeek, {Hesham A.} and Cardozo, {Christopher P.}",
year = "2019",
month = "9",
day = "15",
doi = "10.1089/neu.2018.6144",
language = "English (US)",
volume = "36",
pages = "2722--2731",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "18",

}

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85071785595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071785595&partnerID=8YFLogxK

U2 - 10.1089/neu.2018.6144

DO - 10.1089/neu.2018.6144

M3 - Article

VL - 36

SP - 2722

EP - 2731

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 18

ER -