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|Title:||Leucine-rich diet induces a shift in tumour metabolism from glycolytic towards oxidative phosphorylation, reducing glucose consumption and metastasis in Walker-256 tumour-bearing rats|
|Author:||Viana, Lais Rosa|
Brandt Busanello, Estela Natacha
Marques, Ana Carolina
de Oliveira, Andre Gustavo
Lima, Tanes I.
Castelucci, Bianca Gazieri
Ramos, Celso Dario
Brunetto, Sergio Q.
Silveira, Leonardo Reis
Vercesi, Anibal Eugenio
Consonni, Silvio Roberto
Cintra Gomes-Marcondes, Maria Cristina
|Abstract:||Leucine can stimulate protein synthesis in skeletal muscle, and recent studies have shown an increase in leucine-related mitochondria! 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 (F-18-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 (F-18-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 mitochondria! 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.|
|Appears in Collections:||IB - Artigos e Outros Documentos|
FCM - Artigos e Outros Documentos
CEB - Artigos e Outros Documentos
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