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Leucine‐rich diet changes tumor metabolism, reducing glucose consumption and metastasis in Walker 256 tumor‐bearing rats

Leucine stimulates muscle protein synthesis and is begin used as a potential treatment for muscle wasting conditions, such as cancer cachexia. However, the effects of leucine in the tumor tissue are still unknown. We aimed to describe the effects of a leucine‐rich diet on the Walker 256 tumor tissue. For this purpose, tumor‐bearing Wistar rats were randomly distributed into a control group (normoprotein diet) and leucine group (leucine‐rich diet (18% protein + 3% leucine)). After 20 days of tumor inoculation, the animals underwent to 18F‐FDG PET‐CT and after being euthanized, fresh tumor biopsies were collected to measure the oxygen consumption rate and fixed for electron microscopy analysis. Our results showed that the leucine‐rich diet leads to a lower tumor glucose (18F‐FDG) uptake by tumor and reduced number of metastases sites. Furthermore, leucine‐rich diet changed the mitochondrial morphology and function (from a glycolytic to an oxidative phenotype), associated with a higher gene expression of oxidative phosphorylation components. In addition, tumor tissue from leucine group showed a higher number of apoptotic nuclei with an increased oxidative stress. In conclusion, leucine‐enriched diet was associated with considerable metabolic activity reduction of malignant tissue associated with mitochondrial morphology and function changes in Walker 256 tumor tissue.