Document Detail


Murine intramyocellular lipids quantified by NMR act as metabolic biomarkers in burn trauma.
MedLine Citation:
PMID:  18506378     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It has been suggested that intramyocellular lipids (IMCLs) may serve as biomarkers of insulin resistance and mitochondrial dysfunction. Using a hind-limb mouse model of burn trauma, we tested the hypothesis that severe localized burn trauma involving 5% of the total body surface area causes a local increase in IMCLs in the leg skeletal muscle. We quantified IMCLs from ex vivo intact tissue specimens using High-Resolution Magic Angle Spinning (HRMAS) 1H NMR and characterized the accompanying gene expression patterns in burned versus control skeletal muscle specimens. We also quantified plasma-free fatty acids (FFAs) in burn versus control mice. Our results from HRMAS 1H NMR measurements indicated that IMCL levels were significantly increased in mice exposed to burn trauma. Furthermore, plasma FFA levels were also significantly increased, and gene expression of Glut4, insulin receptor substrate 1 (IRS1), glycolytic genes, and PGC-1beta was downregulated in these mice. Backward stepwise multiple linear regression analysis demonstrated that IMCL levels correlated significantly with FFA levels, which were a significant predictor of IRS1 and PGC-1beta gene expression. We conclude from these findings that IMCLs can serve as metabolic biomarkers in burn trauma and that FFAs and IMCLs may signal altered metabolic gene expression. This signaling may result in the observed burn-induced insulin resistance and skeletal muscle mitochondrial dysfunction. We believe that IMCLs may therefore be useful biomarkers in predicting the therapeutic effectiveness of hypolipidemic agents for patients with severe burns.
Authors:
A Aria Tzika; Loukas G Astrakas; Haihui Cao; Dionyssios Mintzopoulos; Qunhao Zhang; Katie Padfield; Hongue Yu; Michael N Mindrinos; Laurence G Rahme; Ronald G Tompkins
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  21     ISSN:  1107-3756     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-28     Completed Date:  2008-07-23     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  825-32     Citation Subset:  IM    
Affiliation:
NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. atzika@partners.org
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / genetics,  metabolism
Animals
Biological Markers / analysis*,  blood
Body Surface Area
Burns / genetics,  metabolism*,  pathology
Fatty Acids, Nonesterified / analysis,  blood,  metabolism
Gene Expression Profiling
Glucose Transporter Type 4 / genetics,  metabolism
Glycolysis
Hindlimb / metabolism,  pathology
Humans
Insulin Receptor Substrate Proteins
Insulin Resistance
Lipid Metabolism
Lipids / analysis*
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Mice
Mitochondria / metabolism
Models, Biological
Muscle Fibers, Skeletal / metabolism,  pathology
Muscle, Skeletal / metabolism*,  pathology,  ultrastructure
Oligonucleotide Array Sequence Analysis
Regression Analysis
Trans-Activators / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
P50 GM021700/GM/NIGMS NIH HHS; P50GM021700/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Biological Markers; 0/Fatty Acids, Nonesterified; 0/Glucose Transporter Type 4; 0/IRS1 protein, human; 0/Insulin Receptor Substrate Proteins; 0/Irs1 protein, mouse; 0/Lipids; 0/Ppargc1a protein, mouse; 0/Trans-Activators

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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