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.

Autor: 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.; Obesity and Comorbidities Research Centre, 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; Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas, Campinas, SP, Brazil., Castelucci BG; Laboratory of Cytochemistry and Immunocytochemistry, Department of Biochemistry and Tissue Biology. Biology Institute, University of Campinas, Campinas, SP, Brazil., Ramos CD; Division of Nuclear Medicine, Department of Radiology, School of Medical Sciences, 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; Obesity and Comorbidities Research Centre, Biology Institute, University of Campinas, Campinas, SP, Brazil., Vercesi AE; School of Medical Sciences, Department of Clinical Pathology, State University of Campinas, Campinas, SP, Brazil., Consonni SR; Laboratory of Cytochemistry and Immunocytochemistry, Department of Biochemistry and Tissue Biology. Biology Institute, University of Campinas, Campinas, SP, Brazil., Gomes-Marcondes MCC; Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas, Campinas, SP, Brazil. cintgoma@unicamp.br.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Oct 29; Vol. 9 (1), pp. 15529. Date of Electronic Publication: 2019 Oct 29.
DOI: 10.1038/s41598-019-52112-w
Abstrakt: 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 ( 18 F-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 ( 18 F-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.
Databáze: MEDLINE
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