Abstract #1138

Mitochondrial Energy Metabolism in Skeletal Muscle in a Murine Cancer Cachexia Model

Cibely Cristine Fontes De Oliveira¹, Dionyssios Mintzopoulos^2,3, Caterina Constantinou^2,4, Valeria Righi^2,3, Nikolaos Psychogios^3,5, Michael N. Mindrinos⁶, Yong-Ming Yu, Alexander A. Shestov⁷, Ronald G. Tompkins, Francois Lepine⁸, Laurence G. Rahme⁹, Josep M. Argiles¹, Aria A. Tzika^2,3

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.