Serum and Muscle 1H NMR-Based Metabolomics Profiles Reveal Metabolic Changes Influenced by a Maternal Leucine-Rich Diet in Tumor-Bearing Adult Offspring Rats.

Natália Angelo Da Silva Miyaguti,Gabriela Sales Dos Santos,Sarah Christine Pereira De Oliveira,Maria Cristina Cintra Gomes-Marcondes,Danijela Stanisic,Ljubica Tasic,Beatriz Schincariol Manhe

doi:10.3390/nu12072106

Natália Angelo Da Silva Miyaguti, Gabriela Sales Dos Santos + Show 5 more

Open Access

https://doi.org/10.3390/nu12072106

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Journal: Nutrients	Publication Date: Jul 16, 2020
Citations: 6	License type: CC BY 4.0

Affiliation: Universidade Estadual de Campinas

Abstract

A maternal leucine-rich diet showed a positive effect on the gastrocnemius muscle of adult tumor-bearing offspring. To improve the understanding of the metabolic alterations of cancer cachexia and correlate this to preventive treatment, we evaluated the 1H NMR metabolic profiles from serum and gastrocnemius muscle samples of adult Wistar rats. These profiles were initially analyzed, and chemometrics tools were applied to investigate the following groups: C, control group; W, tumor-bearing group; L, the group without tumors and with a maternal leucine-rich diet; WL, the tumor-bearing group with a maternal leucine-rich diet. Tumor growth that led to a high protein breakdown in the W group was correlated to serum metabolites such as tyrosine, phenylalanine, histidine, glutamine, and tryptophan amino acids and uracil. Also, decreased muscle lactate, inversely to serum content, was found in the W group. Conversely, in the WL group, increased lactate in muscle and serum profiles was found, which could be correlated to the maternal diet effect. The muscle lipidomics and NAD+, NADP+, lysine, 4-aminohippurate, and glutamine metabolites pointed to modified energy metabolism and lower muscle mass loss in the WL group. In conclusion, this exploratory metabolomics analyses provided novel insights related to the Walker-256 tumor-bearing offspring metabolism modified by a maternal leucine-rich diet and the next steps in its investigation.

Highlights

Cancer cachexia syndrome is characterized by chronic systemic inflammation and progressive muscle wasting associated or not with fat mass loss
A serum representative spectrum is presented in Figure S1, and the Table S1 corresponds to the metabolites assignment and respective chemical shifts
The differences found in serum during the initial spectral analysis showed higher peak intensity of lactate (1.33 ppm), tyrosine (6.92 and 7.19 ppm), histidine (7.09 and 7.34 ppm), phenylalanine (7.32 ppm, 7.53 ppm and 7.72 ppm), and tryptophan

Summary

Introduction

Cancer cachexia syndrome is characterized by chronic systemic inflammation and progressive muscle wasting associated or not with fat mass loss. Nutrients 2020, 12, 2106 to epigenetics marks on the offspring [4,5,6], our study demonstrated that a leucine-rich diet when maternally administered diminished the muscle mass loss in adult offspring tumor-bearing rats. This approach reduced the cachexia negative protein balance, which ameliorated the gastrocnemius muscle protein synthesis and decreased protein degradation, by activating the mechanistic target of rapamycin (mTOR) pathway and maintaining muscle cathepsin H and calpain activities [3]

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