Leucine-Rich Diet Modulates the Metabolomic and Proteomic Profile of Skeletal Muscle during Cancer Cachexia

Bread Cruz, André Oliveira, Lais Rosa Viana, Leisa Lopes-Aguiar, Rafael Canevarolo, Maiara Caroline Colombera, Rafael Rossi Valentim, Fernanda Garcia-Fóssa, Lizandra Maia de Sousa, Bianca Gazieri Castelucci, Sílvio Roberto Consonni, Daniel Martins-de-Souza, Marcelo Bispo de Jesus, Steven Thomas Russell, Maria Cristina Cintra Gomes-Mardondes

Research output: Contribution to journalArticlepeer-review


Background: Cancer-cachexia induces a variety of metabolic disorders, including skeletal muscle imbalance. Alternative therapy, as nutritional supplementation with leucine, shows a modulatory effect over tumour damage in vivo and in vitro. Method: Adult rats distributed into Control (C), Walker tumour-bearing (W), control fed a leucine-rich diet (L), and tumour-bearing fed a leucine-rich diet (WL) groups had the gastrocnemius muscle metabolomic and proteomic assays performed in parallel to in vitro assays. Results: W group presented an affected muscle metabolomic and proteomic profile mainly related to energy generation and carbohydrates catabolic processes, but leucine-supplemented group (WL) recovered the energy production. In vitro assay showed that cell proliferation, mitochondria number and oxygen consumption were higher under leucine effect than the tumour influence. Muscle proteomics results showed that the main affected cell component was mitochondria, leading to an impacted energy generation, including impairment in proteins of the tricarboxylic cycle and carbohydrates catabolic processes, which were modulated and improved by leucine treatment. Conclusion: In summary, we showed a beneficial effect of leucine upon mitochondria, providing information about the muscle glycolytic pathways used by this amino acid, where it can be associated with the preservation of morphometric parameters and consequent protection against the effects of cachexia.
Original languageEnglish
Article number1880
Number of pages25
Issue number7
Publication statusPublished - 13 Jul 2020

Bibliographical note

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).


  • Experimental cachexia
  • Leucine-rich diet
  • Metabolomic
  • Mitochondria dysfunction
  • Proteomic
  • Skeletal muscle


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