Nuclear magnetic resonance in conjunction with functional genomics suggests mitochondrial dysfunction in a murine model of cancer cachexia

Research output: Contribution to journalArticle


Cancer patients commonly suffer from cachexia, a syndrome in which tumors induce metabolic changes in the host that lead to massive loss in skeletal muscle mass. Using a preclinical mouse model of cancer cachexia, we tested the hypothesis that tumor inoculation causes a reduction in ATP synthesis and genome-wide aberrant expression in skeletal muscle. Mice implanted with Lewis lung carcinomas were examined by in vivo 31P nuclear magnetic resonance (NMR). We examined ATP synthesis rate and the expression of genes that play key-regulatory roles in skeletal muscle metabolism. Our in vivo NMR results showed reduced ATP synthesis rate in tumor-bearing (TB) mice relative to control (C) mice, and were cross-validated with whole genome transcriptome data showing atypical expression levels of skeletal muscle regulatory genes such as peroxisomal proliferator activator receptor γ coactivator 1 ß (PGC-1ß), a major regulator of mitochondrial biogenesis and, mitochondrial uncoupling protein 3 (UCP3). Aberrant pattern of gene expression was also associated with genes involved in inflammation and immune response, protein and lipid catabolism, mitochondrial biogenesis and uncoupling, and inadequate oxidative stress defenses, and these effects led to cachexia. Our findings suggest that reduced ATP synthesis is linked to mitochondrial dysfunction, ultimately leading to skeletal muscle wasting and thus advance our understanding of skeletal muscle dysfunction suffered by cancer patients. This study represents a new line of research that can support the development of novel therapeutics in the molecular medicine of skeletal muscle wasting. Such therapeutics would have wide-spread applications not only for cancer patients, but also for many individuals suffering from other chronic or endstage diseases that exhibit muscle wasting, a condition for which only marginally effective treatments are currently available.


  • Caterina Constantinou
  • Cibely Fontes de Oliveira
  • Dionyssios Mintzopoulos
  • Silvia Busquets
  • Jianxin He
  • Meenu Kesarwani
  • Michael N Mindrinos
  • Laurence G Rahme
  • Josep M Argilés
  • A Aria Tzika
External organisations
  • Harvard Medical School
  • University of Barcelona
Research areas and keywords


  • Adenosine Triphosphate, Animals, Cachexia, Genomics, Humans, Magnetic Resonance Spectroscopy, Male, Mice, Mice, Inbred C57BL, Mitochondria, Muscle, Skeletal, Muscular Atrophy, Neoplasm Transplantation, Neoplasms, Random Allocation, Transcription Factors, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)15-24
Number of pages10
JournalInternational Journal of Molecular Medicine
Issue number1
Publication statusPublished - 2011 Jan
Publication categoryResearch
Externally publishedYes