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Modulatory effects of nutritional supplementation with leucine and / or omega-3 polyunsaturated fatty acid on damages effects of cancer in adult-offspring rats

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Miyaguti, Natália Angelo da Silva
Total Authors: 1
Document type: Doctoral Thesis
Institution: Universidade Estadual de Campinas, Instituto de Biologia
Defense date:
Advisor: Maria Cristina Cintra Gomes-Marcondes

Introduction: Cancer is the second cause of death, and cachexia is a syndrome that can affect up to 85% of advanced cancer patients. Since cachexia still remains irreversible it is important new strategies of prevention. Modifications in the maternal diet with the use of nutritional supplementation can alter the metabolic programming of the offspring until adulthood, being an innovative approach to prevent diseases in the offspring adulthood, such as cancer. Studies have shown that the branched-chain amino acid leucine and the fish oils rich in omega-3 polyunsaturated fatty acid, when used as therapeutic approach, can act as modulators of pathophysiological changes related to cachexia. Objectives: Considering the beneficial effects of these supplements, the present study evaluated whether these nutrients, when administered only during gestation and lactation, could also beneficiate the offspring in the adulthood in responses to the cachexia syndrome. Methods: Pregnant Wistar rats received Control diet; Leucine-rich diet (3% L-leucine) and/or Omega-3 diet (containing fish oil rich in omega-3) during gestation (21 days) and lactation (21 days). After weaning, the males offspring began to receive the Control diet until adulthood (120 days), when was inoculated the Walker 256 tumour. For the survival experiment, after tumour inoculation, the animals were followed until natural death. In a new experiment, the animals were followed for 21 days of tumour growth and then euthanized, including the Control groups, from which serum, muscle and liver tissue samples were collected for enzyme activity analysis, biochemical and molecular parameters, 1H RMN metabolomics, muscle protein synthesis and degradation analysis. Results: Modifications related to the effects of tumour on liver function were found, which minimised the oxidative stress in liver of adult offspring rats whose mothers received nutritional supplementation with leucine and/or omega-3, which reflected in improvements of survival in these animals. The metabolism from the offspring maternally supplemented with leucine was altered, minimising the muscle mass loss, with an improved balance between muscle protein synthesis and degradation. Conclusion: The maternally supplemented adult offspring animals had a better response against cachexia damages; thus, the present study first demonstrated this innovative approach against cancer cachexia effects in muscle and liver tissues of adult offspring tumour-bearing rats. Further studies are now ongoing to better understand the epigenetic mechanism involved in these benefits (AU)

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