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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Viana, Lais Rosa [1] ; Tobar, Natalia [2] ; Brandt Busanello, Estela Natacha [3] ; Marques, Ana Carolina [3] ; de Oliveira, Andre Gustavo [4, 1] ; Lima, Tanes I. [4] ; Machado, Gabrielly [1] ; Castelucci, Bianca Gazieri [5] ; Ramos, Celso Dario [2] ; Brunetto, Sergio Q. [2] ; Silveira, Leonardo Reis [4] ; Vercesi, Anibal Eugenio [3] ; Consonni, Silvio Roberto [5] ; Cintra Gomes-Marcondes, Maria Cristina [1]
Total Authors: 14
Affiliation:
[1] Univ Estadual Campinas, Lab Nutr & Canc, Dept Struct & Funct Biol, Inst Biol, Campinas, SP - Brazil
[2] Univ Estadual Campinas, Div Nucl Med, Dept Radiol, Sch Med Sci, Campinas, SP - Brazil
[3] Univ Estadual Campinas, Sch Med Sci, Dept Clin Pathol, Campinas, SP - Brazil
[4] Univ Estadual Campinas, Obes & Comorbid Res Ctr, Inst Biol, Campinas, SP - Brazil
[5] Univ Estadual Campinas, Lab Cytochem & Immunocytochem, Dept Biochem & Tissue Biol, Inst Biol, Campinas, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 9, OCT 29 2019.
Web of Science Citations: 0
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. (AU)

FAPESP's process: 15/21890-0 - Effect of leucine, ketogenic and combined diets in tumor growth, cachectic state and metabolomic systemic profile, muscle and tumor in rats with cancer cachexia (Walker 256 model)
Grantee:Laís Rosa Viana
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 12/06955-0 - Metabolomic and proteomic profile and cell proliferation and apoptosis in Walker tumour-bearing rats under pregnancy hormones and leucine-rich diet
Grantee:Laís Rosa Viana
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 17/02739-4 - Nutrition and cancer: study of molecular, proteomic and metabolomic aspects of experimental model of cachexia
Grantee:Maria Cristina Cintra Gomes Marcondes
Support type: Research Projects - Thematic Grants
FAPESP's process: 14/13334-7 - Nutrition and cancer: metabolomic, and proteomic profile of muscle, placental, fetal, and tumor cell signaling pathways in Walker-256 tumour-bearing pregnant rats submitted to leucine nutritional supplementation
Grantee:Maria Cristina Cintra Gomes Marcondes
Support type: Regular Research Grants