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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)

Grant number: 15/21890-0
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): June 01, 2016
Effective date (End): October 14, 2021
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Maria Cristina Cintra Gomes Marcondes
Grantee:Laís Rosa Viana
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:17/02739-4 - Nutrition and cancer: study of molecular, proteomic and metabolomic aspects of experimental model of cachexia, AP.TEM
Associated scholarship(s):17/20288-0 - Potential of targeting protein breakdown mechanism (specific E3 ubiquitin ligases) in vitro and in vivo models of cachexia/muscle atrophy, BE.EP.PD


Cancer is an important health problem, which still remains raising the number of deaths related to this disease. Cachexia is responsible for 25-30% of all cancer-related deaths. Cancer-cachexia leads to involuntary weight loss, impaired quality of life, and poor prognosis. Nutritional leucine supplementation has been shown to preserve muscle mass in cancer cachectic patients, due to the capacity to increase protein synthesis in skeletal muscle. However, leucine can also stimuli proliferation and motility, potentially enhancing metastasis processess. Cancer cells have a unique metabolism as the abnormal mitochondrial function, which causes mainly glucose and glutamine fermentation by neoplastic cell to produce energy (Warburg effect) and also prevents ketone body utilization as energy source. So, dietary strategies that decrease blood glucose may reduce tumor cell growth and metastasis, reducing the glucose avaible and suppressing insulin signaling. One of these strategies is the Ketogenic diet, which is a high fat (75-85%), moderate protein (10-20%), low carbohydrate (5-10%) diet that reduces glucose (and insulin) and elevates the ketone bodies. The result is depletion of carbohydrate store as glycogen, reducing glucose availability, which suppresses the insulin signaling and elevates blood ketones, all processes associated with lower tumor growth. Although leucine can promote skeletal muscle growth, the effects of leucine in cancer growth and metastasis are still unclear. Therefore, this project aims to evaluate the effects of nutritional ketogenic+leucine supplementation on tumor growth and the cachexia state.

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Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE MATUOKA E CHIOCCHETTI, GABRIELA; LOPES-AGUIAR, LEISA; DA SILVA MIYAGUTI, NATALIA ANGELO; VIANA, LAIS ROSA; SALGADO, CARLA DE MORAES; ORVOEN, OPHELIE OCEAN; FLORINDO, DERLY; DOS SANTOS, ROGERIO WILLIAMS; CINTRA GOMES-MARCONDES, MARIA CRISTINA. A Time-Course Comparison of Skeletal Muscle Metabolomic Alterations in Walker-256 Tumour-Bearing Rats at Different Stages of Life. METABOLITES, v. 11, n. 6, . (17/02739-4, 15/21890-0, 18/20637-7, 19/14803-4, 19/13937-7, 19/20558-2)
MIYAGUTI, NATALIA ANGELO DA SILVA; CHIOCCHETTI, GABRIELA DE MATUOKA E; SALGADO, CARLA DE MORAES; LOPES-AGUIAR, LEISA; VIANA, LAIS ROSA; BLANCHARD, LEA; DOS SANTOS, ROGERIO WILLIANS; GOMES-MARCONDES, MARIA CRISTINA CINTRA. Walker-256 Tumour-Induced Cachexia Altered Liver Metabolomic Profile and Function in Weanling and Adult Rats. METABOLITES, v. 11, n. 12, . (19/14803-4, 19/20558-2, 19/13937-7, 15/21890-0, 17/02739-4, 18/20637-7)
OLIVEIRA, MELINA DE MORAES SANTOS; SALGADO, CARLA DE MORAES; VIANA, LAIS ROSA; GOMES-MARCONDES, MARIA CRISTINA CINTRA. Pregnancy and Cancer: Cellular Biology and Mechanisms Affecting the Placenta. CANCERS, v. 13, n. 7, . (18/20637-7, 17/02739-4, 15/21890-0)
VIANA, LAIS ROSA; LOPES-AGUIAR, LEISA; ROSOLEN, RAFAELA ROSSI; DOS SANTOS, ROGERIO WILLIANS; CINTRA GOMES-MARCONDES, MARIA CRISTINA. H-1-NMR Based Serum Metabolomics Identifies Different Profile between Sarcopenia and Cancer Cachexia in Ageing Walker 256 Tumour-Bearing Rats. METABOLITES, v. 10, n. 4, . (15/21890-0, 12/06955-0, 17/02739-4, 14/13334-7, 19/20558-2)
VIANA, LAIS ROSA; TOBAR, NATALIA; BRANDT BUSANELLO, ESTELA NATACHA; MARQUES, ANA CAROLINA; DE OLIVEIRA, ANDRE GUSTAVO; LIMA, TANES I.; MACHADO, GABRIELLY; CASTELUCCI, BIANCA GAZIERI; RAMOS, CELSO DARIO; BRUNETTO, SERGIO Q.; et al. 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. SCIENTIFIC REPORTS, v. 9, . (15/21890-0, 12/06955-0, 17/02739-4, 14/13334-7)
DE QUADROS, V. P.; TOBAR, N.; VIANA, L. R.; DOS SANTOS, R. W.; KIYATAKA, P. H. M.; GOMES-MARCONDES, M. C. C.. The 17 beta-oestradiol treatment minimizes the adverse effects of protein restriction on bone parameters in ovariectomized Wistar rats RELEVANCE TO OSTEOPOROSIS AND THE MENOPAUSE. BONE & JOINT RESEARCH, v. 8, n. 12, p. 573-581, . (15/21890-0, 17/02739-4, 14/13334-7)

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