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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.
Viana, Laís Rosa; Tobar, Natália; Busanello, Estela Natacha Brandt; Marques, Ana Carolina; de Oliveira, Andre Gustavo; Lima, Tanes I; Machado, Gabrielly; Castelucci, Bianca Gazieri; Ramos, Celso Dario; Brunetto, Sérgio Q; Silveira, Leonardo Reis; Vercesi, Anibal Eugenio; Consonni, Sílvio Roberto; Gomes-Marcondes, Maria Cristina Cintra.
Afiliación
  • Viana LR; Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas, Campinas, SP, Brazil.
  • Tobar N; Division of Nuclear Medicine, Department of Radiology, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
  • Busanello ENB; School of Medical Sciences, Department of Clinical Pathology, State University of Campinas, Campinas, SP, Brazil.
  • Marques AC; School of Medical Sciences, Department of Clinical Pathology, State University of Campinas, Campinas, SP, Brazil.
  • de Oliveira AG; Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas, Campinas, SP, Brazil.
  • Lima TI; Obesity and Comorbidities Research Centre, Biology Institute, University of Campinas, Campinas, SP, Brazil.
  • Machado G; Obesity and Comorbidities Research Centre, Biology Institute, University of Campinas, Campinas, SP, Brazil.
  • Castelucci BG; Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas, Campinas, SP, Brazil.
  • Ramos CD; Laboratory of Cytochemistry and Immunocytochemistry, Department of Biochemistry and Tissue Biology. Biology Institute, University of Campinas, Campinas, SP, Brazil.
  • Brunetto SQ; Division of Nuclear Medicine, Department of Radiology, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
  • Silveira LR; Division of Nuclear Medicine, Department of Radiology, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
  • Vercesi AE; Obesity and Comorbidities Research Centre, Biology Institute, University of Campinas, Campinas, SP, Brazil.
  • Consonni SR; School of Medical Sciences, Department of Clinical Pathology, State University of Campinas, Campinas, SP, Brazil.
  • Gomes-Marcondes MCC; Laboratory of Cytochemistry and Immunocytochemistry, Department of Biochemistry and Tissue Biology. Biology Institute, University of Campinas, Campinas, SP, Brazil.
Sci Rep ; 9(1): 15529, 2019 10 29.
Article en En | MEDLINE | ID: mdl-31664147
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosforilación Oxidativa / Carcinoma 256 de Walker / Glucosa / Glucólisis / Leucina Límite: Animals Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosforilación Oxidativa / Carcinoma 256 de Walker / Glucosa / Glucólisis / Leucina Límite: Animals Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido