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.
Keywords