Proton NMR spectroscopy shows lipids accumulate in skeletal muscle in response to burn trauma-induced apoptosis.
Burn trauma triggers hypermetabolism and muscle wasting via increased cellular protein degradation and apoptosis. Proton nuclear magnetic resonance (1H NMR) spectroscopy can detect mobile lipids in vivo. To examine the local effects of burn in skeletal muscle, we performed in vivo 1H NMR on mice 3 days after burn trauma; and ex vivo, high-resolution, magic angle spinning (1)H NMR on intact excised mouse muscle samples before and 1 and 3 days after burn. These samples were then analyzed for apoptotic nuclei using a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. To confirm our NMR and cell biology results, we used transcriptome analysis to demonstrate that burn trauma alters the expression of genes involved in lipid metabolism and apoptosis. Our results demonstrate that burn injury results in a localized intramyocellular lipid accumulation, which in turn is accompanied by burn-induced apoptosis and mitochondrial dysfunction, as seen by the up-regulation of apoptotic genes and down-regulation of genes that encode lipid oxidation and the peroxisomal proliferator activator receptor gamma coactivator PGC-1beta. Moreover, the increased levels of bisallylic methylene fatty acyl protons (2.8 ppm) and vinyl protons (5.4 ppm), in conjunction with the TUNEL assay results, further suggest that burn trauma results in apoptosis. Together, our results provide new insight into the local physiological changes that occur in skeletal muscle after severe burn trauma.
Astrakas
Loukas G
LG
Department of Surgery, Massachusetts General Hospital, Shriners Burns Institute and Harvard Medical School, Boston, Massachusetts 02114, USA.
Goljer
Igor
I
Yasuhara
Shingo
S
Padfield
Katie E
KE
Zhang
Qunhao
Q
Gopalan
Suresh
S
Mindrinos
Michael N
MN
Dai
George
G
Yu
Yong-Ming
YM
Martyn
J A Jeevendra
JA
Tompkins
Ronald G
RG
Rahme
Laurence G
LG
Tzika
A Aria
AA
D017209:Apoptosis; D002056:Burns / Q000378:metabolism* / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D020287:In Situ Nick-End Labeling; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction
D005227:Fatty Acids