Cibely Cristine Fontes De Oliveira1,
Dionyssios Mintzopoulos2,3, Caterina Constantinou2,4,
Valeria Righi2,3, Nikolaos Psychogios3,5, Michael N.
Mindrinos6, Yong-Ming Yu, Alexander A. Shestov7, Ronald
G. Tompkins, Francois Lepine8, Laurence G. Rahme9,
Josep M. Argiles1, Aria A. Tzika2,3
1Cancer Research Group,
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Barcelona, Spain; 2NMR Surgical
Laboratory, Department of Surgery, Massachusetts General Hospital &
Shriners Burn Institute, Harvard Medical School, Boston, MA, United States; 3Department
of Radiology, Athinoula A. Martinos Center for Biomedical Imaging,
Massachusetts General Hospital, Charlestown, MA, United States; 4Molecular
Surgery Laboratory, Massachusetts General Hospital & Shriners Burn
Institute, Harvard Medical School, Boston, MA, United States; 5Dept.
of Surgery, Massachusetts General Hospital, Boston, MA, United States; 6Department
of Biochemistry, School of Medicine, Stanford University, Stanford, CA,
United States; 7Center for Magnetic Resonance Research, Department
of Radiology, University of Minnesota Medical School, Minneapolis, MN, United
States; 8Institut National de la Recherche Scientifique-Institut
Armand-Frappier, Quebec, QC, Canada; 9Molecular Surgery
Laboratory, Department of Surgery, Massachusetts General Hospital &
Shriners Burn Institute, Harvard Medical School, Boston, MA, United States
We employed in vivo P31 NMR on intact mice and mass spectrometry in skeletal muscle samples, in a mouse cancer (Lewis lung carcinoma) cachexia model. ATP synthesis rate by P31 NMR and TCA cycle flux by mass spectrometry were significantly reduced by 47% and 25% respectively in cancer-bearing mice (P<0.03; t-test). The ratio of ATP synthesis rate to the TCA cycle flux, which provides an index of mitochondrial coupling, was 30% less in cancer-bearing mice (P<0.05; t-test). Our results were cross-validated with genomic analysis, showing aberrant expression levels in key regulatory genes and by electron microscopy showing abnormal giant mitochondria.