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

• Main Authors: Natália Angelo da Silva Miyaguti, Danijela Stanisic, Sarah Christine Pereira de Oliveira, Gabriela Sales dos Santos, Beatriz Schincariol Manhe, Ljubica Tasic, Maria Cristina Cintra Gomes-Marcondes
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Nutrients
• Subjects: cancer; cachexia; leucine; maternal nutrition; metabolomics; muscle wasting
• Online Access: https://www.mdpi.com/2072-6643/12/7/2106

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.