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1H NMR metabolomic and transcriptomic analyses reveal urinary metabolites as biomarker candidates in response to protein undernutrition in adult rats

Published online by Cambridge University Press:  20 August 2020

Yosuke Komatsu
Affiliation:
Graduate School of Life Science, Hokkaido University, Sapporo, Hokkaido 060-0810, Japan Center for Food and Medical Innovation Promotion, Institute for the Promotion of Business-Regional Collaboration of Hokkaido University, Sapporo, Hokkaido 001-0021, Japan Wellness & Nutrition Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa 252-8583, Japan
Yasuaki Wada
Affiliation:
Center for Food and Medical Innovation Promotion, Institute for the Promotion of Business-Regional Collaboration of Hokkaido University, Sapporo, Hokkaido 001-0021, Japan Wellness & Nutrition Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa 252-8583, Japan
Hirohisa Izumi
Affiliation:
Center for Food and Medical Innovation Promotion, Institute for the Promotion of Business-Regional Collaboration of Hokkaido University, Sapporo, Hokkaido 001-0021, Japan Wellness & Nutrition Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa 252-8583, Japan
Takashi Shimizu
Affiliation:
Wellness & Nutrition Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa 252-8583, Japan
Yasuhiro Takeda
Affiliation:
Wellness & Nutrition Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa 252-8583, Japan
Tomoyasu Aizawa
Affiliation:
Graduate School of Life Science, Hokkaido University, Sapporo, Hokkaido 060-0810, Japan Department of Advanced Transdisciplinary Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Hokkaido 060-0810, Japan Global Station for Soft Matter, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, Hokkaido 060-0810, Japan
Corresponding

Abstract

Protein undernutrition contributes to the development of various diseases in broad generations. Urinary metabolites may serve as non-invasive biomarkers of protein undernutrition; however, this requires further investigation. We aimed to identify novel urinary metabolites as biomarker candidates responsive to protein undernutrition. Adult rats were fed control (CT; 14 % casein) or isoenergetic low-protein (LP; 5 % casein) diets for 4 weeks. 1H NMR metabolomics was applied to urine, plasma and liver samples to identify metabolites responsive to protein undernutrition. Liver samples were subjected to mRNA microarray and quantitative PCR analyses to elucidate the mechanisms causing fluctuations in identified metabolites. Urinary taurine levels were significantly lower in the LP group than in the CT group at week 1 and remained constant until week 4. Hepatic taurine level and gene expression level of cysteine dioxygenase type 1 were also significantly lower in the LP group than in the CT group. Urinary trimethylamine N-oxide (TMAO) levels were significantly higher in the LP group than in the CT group at week 2 and remained constant until week 4. Hepatic TMAO level and gene expression levels of flavin-containing mono-oxygenase 1 and 5 were also significantly higher in the LP group than in the CT group. In conclusion, urinary taurine and TMAO levels substantially responded to protein undernutrition. Furthermore, changes in hepatic levels of these metabolites and gene expressions associated with their metabolic pathways were also reflected in their fluctuating urinary levels. Thus, taurine and TMAO could act as non-invasive urinary biomarker candidates to detect protein undernutrition.

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Full Papers
Copyright
© The Author(s), 2020. Published by Cambridge University Press on behalf of The Nutrition Society

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1H NMR metabolomic and transcriptomic analyses reveal urinary metabolites as biomarker candidates in response to protein undernutrition in adult rats
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