Effects of nutritional supplementation with leucine in serum and tumour metabolic profile of Walker 256-tumour bearing rats

Author(s)

Laís Rosa Viana

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2015-11-12

Examining board members

Maria Cristina Cintra Gomes Marcondes; Miguel Arcanjo Areas; Celine Fernandes Bernardes; Alexandre Gabarra de Oliveira; Antonio Carlos Boschero

• Advisor: Maria Cristina Cintra Gomes Marcondes

Abstract

Cancer is a worldwide problem, and the number of deaths related to this disease continues to rise. One of the major factors that lead to death in cancer is cachexia, which handles 25¿30% of all cancer-related deaths. Cancer cachexia is a complex metabolic and nutritional syndrome characterised by involuntary weight loss, mainly due to muscle tissue wasting, leading to less mobility, impaired quality of life, and survival added to poor prognosis. Dietary supplementation can potentially reduce the effects of cancer cachexia. One of these dietary supplements is leucine, which is a branched-chain amino acid (BCAAs) that also acts as a cell signalling, leading to preserve muscle mass in cancer cachectic patients. Leucine activates the mammalian target of rapamycin complex 1 (mTORC1), which is an important regulator of protein synthesis, increasing the protein synthesis in skeletal muscle. However, mTOR signalling also promotes cell proliferation and motility, which could potentially enhance the metastasis. Thus, it is important to determine whether leucine also activates mTOR in tumour tissue. Metabolomics allows the identification and quantification of several metabolites with high precision; which allows the better understanding of the mechanisms of biological and biochemical processes in complex systems, such as cancer cachexia. We consider the metabolomics a good strategy for the identification of metabolites under the effects of leucine supplementation. Therefore, the aim of this study was to analyse the metabolomic derangements in serum and Walker-256 tumour tissue in rats under the modulatory effect of a leucine-rich diet. For this purpose, female Wistar rats were distributed into four experimental groups: C, control group; W, Walker 256 tumour-bearing group; L, leucine control group; LW, Walker 256 tumour-bearing group. We assessed metabolomic profiles of serum and tumour tissue, tumour proliferation and protein synthesis pathways. Among the 58 serum metabolites identified, 11 were changed in W group and 25 metabolites changed in LW group, suggesting a different impact on metabolic pathways between both tumour-bearing groups. The changes found in this study shows changes in the process related to protein metabolism in the W group and that this altered pathways were modulated in tumor-bearing rats fed with leucine-rich diet. We found increase in the synthesis and degradation of ketone bodies, suggesting possible mobilization and redirection of ketone bodies to the tumor in the LW group. Taking all results, we conclude that nutritional supplementation with leucine causes metabolic modulation which can favor the mobilization and utilization of energy sources by most host tissues, and jeopardizes the tumour tissue since cancer cells has reduce ability to metabolize ketone bodies for their own energy supply (AU)

• 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 Opportunities: Scholarships in Brazil - Doctorate