Muscle and serum metabolomes are dysregulated in colon-26 tumor-bearing mice despite amelioration of cachexia with activin receptor type 2B ligand blockade

: Lautaoja JH, Lalowski M, Nissinen TA, Hentilä J, Shi Y, Ritvos O, Cheng S, Hulmi JJ

: 2019

: American Journal of Physiology : Endocrinology and Metabolism

: American journal of physiology. Endocrinology and metabolism

: Am J Physiol Endocrinol Metab

: 316

: 5

: E852

: E865

: 14

: 0193-1849

: 1522-1555

DOI: https://doi.org/10.1152/ajpendo.00526.2018

) nucleotide-related intermediates. Muscle metabolomics revealed increased content of free phenylalanine in cancer that strongly correlated with the loss of body mass within the last 2 days of the experiment. This correlation was also detected in serum. Decreased ribosomal RNA content and phosphorylation of a marker of pyrimidine synthesis revealed changes in nucleotide metabolism in cancer. Overall, the effect of the experimental C26 cancer predominated over blocking ACVR2B ligands in both muscle and serum. However, the level of methyl phosphate, which was decreased in muscle in cancer, was restored by sACVR2B-Fc treatment. In conclusion, experimental cancer affected muscle and blood metabolomes mostly independently of blocking ACVR2B ligands. Of the affected metabolites, we have identified free phenylalanine as a promising biomarker of muscle atrophy or cachexia. Finally, the decreased capacity for pyrimidine nucleotide and protein synthesis in tumor-bearing mice opens up new avenues in cachexia research.