Leucine can stimulate
protein synthesis in skeletal muscle, and recent studies have shown an increase in
leucine-related mitochondrial biogenesis and oxidative phosphorylation capacity in muscle cells. However,
leucine-related effects in tumour tissues are still poorly understood. Thus, we described the effects of
leucine in both in vivo and in vitro models of a Walker-256 tumour. Tumour-bearing Wistar rats were randomly distributed into a control group (W; normoprotein diet) and
leucine group (LW;
leucine-rich diet [normoprotein + 3%
leucine]). After 20 days of tumour evolution, the animals underwent 18-fludeoxyglucose positron emission computed tomography (18F-FDG PET-CT) imaging, and after
euthanasia, fresh tumour biopsy samples were taken for oxygen consumption rate measurements (Oroboros Oxygraph), electron microscopy analysis and
RNA and
protein extraction. Our main results from the LW group showed no tumour size change, lower tumour
glucose (18F-FDG) uptake, and reduced metastatic sites. Furthermore,
leucine stimulated a shift in tumour metabolism from glycolytic towards oxidative phosphorylation, higher
mRNA and
protein expression of oxidative phosphorylation components, and enhanced mitochondrial density/area even though the
leucine-treated tumour had a higher number of apoptotic nuclei with increased oxidative stress. In summary, a
leucine-rich diet directed Walker-256 tumour metabolism to a less glycolytic phenotype profile in which these metabolic alterations were associated with a decrease in tumour aggressiveness and reduction in the number of metastatic sites in rats fed a diet supplemented with this
branched-chain amino acid.