Dionyssios Mintzopoulos1,2, Cibely Cristine Fontes de Oliveira3, Jianxin He4, Caterina Constantinou4, Michael N. Mindrinos5, Laurence G. Rahme4, Josep M. Argiles3, A Aria Tzika1,2
1NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, United States; 2Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, United States; 3Cancer Research Group, Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain; 4Molecular Surgery Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, United States; 5Stanford Genome Technology Center, Department of Biochemistry, Stanford University School of Medicine, Palo Alto, CA, United States
We employed in vivo P31 NMR on intact mice, in a mouse cancer (Lewis lung carcinoma) cachexia model. We examined ATP synthesis rate and the gene expression of key regulatory genes, involved in regulation of skeletal muscle metabolism. Our in vivo NMR results that showed significantly reduced rate of ATP synthesis rate were cross-validated with genomic analysis, showing aberrant expression levels in key regulatory genes. Our findings implicate that reduction in ATP synthesis rate is linked to mitochondrial dysfunction leading to wasting of skeletal muscle in cancer cachexia.