Cutaneous burn injury alters relative tricarboxylic acid cycle fluxes in rat liver.
Severe injury induces a hypermetabolic state in the liver; however, the pathways that are responsible for the increase in hepatic energy demand have not been identified. Relative fluxes in the tricarboxylic acid (TCA) cycle were determined in perfused livers from rats 4 days after administration of a cutaneous burn injury. The perfusate was supplemented with 5 mM uniformly labeled 13C-lactate to efficiently label intracellular metabolites. Flux ratios were calculated on the basis of (1) the 13C-labeling pattern of the glutamate and lactate isotopomers within the liver as determined by nuclear magnetic resonance spectroscopy and (2) an isotopomer mass balance model of the TCA cycle. Calculated flux ratios suggest that burn injury results in an increase in the contribution of pyruvate to the oxaloacetate pool at the expense of non-TCA cycle sources. Furthermore, a dramatic increase in 13C-labeling of glucose was observed in burned rat livers. These data taken together suggest that burn injury induces intrinsic changes in intrahepatic metabolism, including an alteration of the relative fluxes consistent with increased gluconeogenesis from lactate.
Yarmush
D M
DM
Center for Engineering in Medicine, Massachusetts General Hospital, Boston, USA.
MacDonald
A D
AD
Foy
B D
BD
Berthiaume
F
F
Tompkins
R G
RG
Yarmush
M L
ML
D000818:Animals; D002056:Burns / Q000150:complications*; D002247:Carbon Isotopes; D002952:Citric Acid Cycle / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley
D002247:Carbon Isotopes; D005947:Glucose