Viana Laís Rosa, Lopes-Aguiar Leisa, Rossi Rosolen Rafaela, Willians Dos Santos Rogerio, Cintra Gomes-Marcondes Maria Cristina
Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas (UNICAMP), Campinas 13083862, Brazil.
Metabolites. 2020 Apr 21;10(4):161. doi: 10.3390/metabo10040161.
Sarcopenia among the older population has been growing over the last few years. In addition, the incidence of cancers increases with age and, consequently, the development of cachexia related cancer. Therefore, the elucidation of the metabolic derangements of sarcopenia and cachexia are important to improve the survival and life quality of cancer patients. We performed the H-NMR based serum metabolomics in adult (A) and ageing (S) Walker 256 tumour-bearing rats in different stages of tumour evolution, namely intermediated (Wi) and advanced (Wa). Among 52 serum metabolites that were identified, 21 were significantly increased in S and 14 and 19 decreased in the Wi and Wa groups, respectively. The most impacted pathways by this metabolic alteration were related by amino acid biosynthesis and metabolism, with an upregulation in S group and downregulation in Wi and Wa groups. Taken together, our results suggest that the increase in metabolic profile in ageing rats is associated with the higher muscle protein degradation that releases several metabolites, especially amino acids into the serum. On the other hand, we hypothesise that the majority of metabolites released by muscle catabolism are used by tumours to sustain rapid cell proliferation and tumorigenesis.
在过去几年中，老年人群中的肌肉减少症一直在增加。此外，癌症的发病率随年龄增长而上升，因此，与癌症相关的恶病质也在发展。所以，阐明肌肉减少症和恶病质的代谢紊乱对于提高癌症患者的生存率和生活质量很重要。我们对成年（A）和老龄（S）携带Walker 256肿瘤的大鼠在肿瘤发展的不同阶段，即中期（Wi）和晚期（Wa），进行了基于氢核磁共振的血清代谢组学研究。在鉴定出的52种血清代谢物中，有21种在S组中显著增加，在Wi组和Wa组中分别有14种和19种减少。这种代谢改变影响最大的途径与氨基酸生物合成和代谢有关，S组上调，Wi组和Wa组下调。综上所述，我们的结果表明，老龄大鼠代谢谱的增加与较高的肌肉蛋白质降解有关，肌肉蛋白质降解会释放多种代谢物，尤其是氨基酸进入血清。另一方面，我们推测肌肉分解代谢释放的大多数代谢物被肿瘤用来维持快速的细胞增殖和肿瘤发生。
