Leucine‐rich diet minimises liver glycogen mobilisation and modulates liver gluconeogenesis enzyme expression in tumour‐bearing cachectic rats

Abstract

AbstractAimsCachexia 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 ResultsWistar 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.ConclusionsOur 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.