Leucine-Rich Diet Improved Muscle Function in Cachectic Walker 256 Tumour-Bearing Wistar Rats
Laís Rosa Viana,
Gabriela de Matuoka e Chiocchetti,
Lucas Oroy,
Willians Fernando Vieira,
Estela Natacha Brandt Busanello,
Ana Carolina Marques,
Carla de Moraes Salgado,
Alexandre Leite Rodrigues de Oliveira,
André Schwambach Vieira,
Paula Saenz Suarez,
Lizandra Maia de Sousa,
Bianca Gazieri Castelucci,
Anibal Eugenio Vercesi,
Sílvio Roberto Consonni,
Maria Cristina Cintra Gomes-Marcondes
Affiliations
Laís Rosa Viana
Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil
Gabriela de Matuoka e Chiocchetti
Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil
Lucas Oroy
Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil
Willians Fernando Vieira
Laboratory of Nerve Regeneration, Department of Structural and Functional Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil
Estela Natacha Brandt Busanello
School of Medical Sciences, Department of Clinical Pathology, University of Campinas—UNICAMP, Campinas 13083-970, SP, Brazil
Ana Carolina Marques
School of Medical Sciences, Department of Clinical Pathology, University of Campinas—UNICAMP, Campinas 13083-970, SP, Brazil
Carla de Moraes Salgado
Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil
Alexandre Leite Rodrigues de Oliveira
Laboratory of Nerve Regeneration, Department of Structural and Functional Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil
André Schwambach Vieira
Laboratory of Electrophysiology, Neurobiology and Behaviour—LENC, Department of Structural and Functional Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil
Paula Saenz Suarez
Laboratory of Cytochemistry and Immunocytochemistry, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil
Lizandra Maia de Sousa
Laboratory of Cytochemistry and Immunocytochemistry, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil
Bianca Gazieri Castelucci
Laboratory of Cytochemistry and Immunocytochemistry, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil
Anibal Eugenio Vercesi
School of Medical Sciences, Department of Clinical Pathology, University of Campinas—UNICAMP, Campinas 13083-970, SP, Brazil
Sílvio Roberto Consonni
Laboratory of Cytochemistry and Immunocytochemistry, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil
Maria Cristina Cintra Gomes-Marcondes
Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil
Skeletal muscle atrophy occurs in several pathological conditions, such as cancer, especially during cancer-induced cachexia. This condition is associated with increased morbidity and poor treatment response, decreased quality of life, and increased mortality in cancer patients. A leucine-rich diet could be used as a coadjutant therapy to prevent muscle atrophy in patients suffering from cancer cachexia. Besides muscle atrophy, muscle function loss is even more important to patient quality of life. Therefore, this study aimed to investigate the potential beneficial effects of leucine supplementation on whole-body functional/movement properties, as well as some markers of muscle breakdown and inflammatory status. Adult Wistar rats were randomly distributed into four experimental groups. Two groups were fed with a control diet (18% protein): Control (C) and Walker 256 tumour-bearing (W), and two other groups were fed with a leucine-rich diet (18% protein + 3% leucine): Leucine Control (L) and Leucine Walker 256 tumour-bearing (LW). A functional analysis (walking, behaviour, and strength tests) was performed before and after tumour inoculation. Cachexia parameters such as body weight loss, muscle and fat mass, pro-inflammatory cytokine profile, and molecular and morphological aspects of skeletal muscle were also determined. As expected, Walker 256 tumour growth led to muscle function decline, cachexia manifestation symptoms, muscle fibre cross-section area reduction, and classical muscle protein degradation pathway activation, with upregulation of FoxO1, MuRF-1, and 20S proteins. On the other hand, despite having no effect on the walking test, inflammation status or muscle oxidative capacity, the leucine-rich diet improved muscle strength and behaviour performance, maintained body weight, fat and muscle mass and decreased some protein degradation markers in Walker 256 tumour-bearing rats. Indeed, a leucine-rich diet alone could not completely revert cachexia but could potentially diminish muscle protein degradation, leading to better muscle functional performance in cancer cachexia.
