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

Abstract

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.

Publication DOI: https://doi.org/10.3390/cancers12071880
Divisions: College of Health & Life Sciences > School of Biosciences
Additional Information: © 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/).
Uncontrolled Keywords: Experimental cachexia,Leucine-rich diet,Metabolomic,Mitochondria dysfunction,Proteomic,Skeletal muscle,Oncology,Cancer Research
Full Text Link:
Related URLs: https://www.mdp ... -6694/12/7/1880 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2020-07-13
Accepted Date: 2020-07-06
Authors: Cruz, Bread
Oliveira, André
Viana, Lais Rosa
Lopes-aguiar, Leisa
Canevarolo, Rafael
Colombera, Maiara Caroline
Valentim, Rafael Rossi
Garcia-fóssa, Fernanda
De Sousa, Lizandra Maia
Castelucci, Bianca Gazieri
Consonni, Sílvio Roberto
Martins-de-souza, Daniel
De Jesus, Marcelo Bispo
Russell, Steven Thomas (ORCID Profile 0000-0002-5491-900X)
Gomes-mardondes, Maria Cristina Cintra

Download

[img]

Version: Published Version

License: Creative Commons Attribution

| Preview

Export / Share Citation


Statistics

Additional statistics for this record