BackgroundCachexia is one of the most important causes of cancer-related death. Supplementation with branched-chain amino acids, particularly leucine, has been used to minimise loss of muscle tissue, although few studies have examined the effect of this type of nutritional supplementation on the metabolism of the tumour-bearing host. Therefore, the present study evaluated whether a leucine-rich diet affects metabolomic derangements in serum and tumour tissues in tumour-bearing Walker-256 rats (providing an experimental model of cachexia).MethodsAfter 21 days feeding Wistar female rats a leucine-rich diet, distributed in L-leucine and LW-leucine Walker-256 tumour-bearing groups, we examined the metabolomic profile of serum and tumour tissue samples and compared them with samples from tumour-bearing rats fed a normal protein diet (C – control; W – tumour-bearing groups). We utilised 1H-NMR as a means to study the serum and tumour metabolomic profile, tumour proliferation and tumour protein synthesis pathway.ResultsAmong the 58 serum metabolites examined, we found that 12 were altered in the tumour-bearing group, reflecting an increase in activity of some metabolic pathways related to energy production, which diverted many nutrients toward tumour growth. Despite displaying increased tumour cell activity (i.e., higher Ki-67 and mTOR expression), there were no differences in tumour mass associated with changes in 23 metabolites (resulting from valine, leucine and isoleucine synthesis and degradation, and from the synthesis and degradation of ketone bodies) in the leucine-tumour group. This result suggests that the majority of nutrients were used for host maintenance.ConclusionA leucine rich-diet, largely used to prevent skeletal muscle loss, did not affect Walker 256 tumour growth and led to metabolomic alterations that may partially explain the positive effects of leucine for the whole tumour-bearing host.

Aims Cachexia is defined as a complex metabolic syndrome that is associated with tissue damage. Some studies have shown that the liver metabolic alterations contribute to overall host tissue wasting. Knowing that leucine acts as cell signalling, we evaluated hepatic metabolism in Walker 256 tumour‐bearing rats and investigated the modulatory effects of a leucine‐rich diet. Methods and Results Wistar rats were distributed into 4 groups: control (C) and tumour‐bearing (W) groups, fed a control diet, and leucine (L) and leucine tumour‐bearing (LW) groups, which fed a leucine‐rich diet. After tumour evolution (21 days), liver samples were collected, and assessed the glycogen content via histological periodic acid‐Schiff (PAS) staining and performed the molecular and biochemical analysis. A higher liver‐to‐body weight rate was observed in W and LW groups, whereas a lower muscle‐to‐body weight ratio was observed only in W group. Hepatic glycogen content was lower only in W group, which had a greater number of hepatocyte nuclei; these parameters were unchanged in LW rats. Moreover, phosphoenolpyruvate carboxykinase (PEPCK), glycogen synthase, and lactate dehydrogenase (LDHA) gene expressions were higher in liver tissue from W group than in LW group. However, liver alkaline phosphatase and γGT activities, and also liver AMP‐activated protein kinase (AMPK) expression were higher in both tumour‐bearing groups. Conclusions Our results suggest that a leucine‐rich diet has a protective effect on the loss of skeletal muscle and also minimises the liver failure induced by Walker 256 tumours. Despite the lack of protection against liver damage, the leucine‐rich diet modulated liver energy stores, likely decreasing the futile Cori cycle and reducing energy expenditures.