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

ABSTRACT: 1H NMR metabolomics was performed on urine samples weekly and on plasma and liver samples collected at week 4 from these animals, to identify metabolites that respond to protein undernutrition. To further investigate metabolites which were fluctuated in response to protein undernutrition in terms of metabolic enzymes, hepatic mRNA microarray and quantitative PCR analyses were also performed at week 4.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE144207 | GEO | 2020/01/25

REPOSITORIES: GEO

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Project description:BACKGROUND: Protein undernutrition is prevalent mainly among elderly people, and it could develop diseases such as sarcopenia. Urinary metabolites may become biomarkers reflecting protein undernutrition, but this has been insufficiently investigated.OBJECTIVE: The purpose of this study was to identify novel urinary metabolites as biomarker candidates responsive to protein undernutrition.METHODS: Adult male Wistar rats were fed an AIN-93 M diet [14% casein, control (CT) diet] or an AIN-93 M-based isocaloric diet [5% casein, low protein (LP) diet] for 4 weeks. 1H nuclear magnetic resonance metabolomic analysis was performed on urine samples weekly and on plasma and liver samples at week 4 to identify metabolites that respond to protein undernutrition. Liver samples were also subjected to mRNA microarray and quantitative PCR analyses at week 4 to investigate alterations of the gene expressions responsive to protein undernutrition.RESULTS: Urinary taurine levels were significantly lower in the LP group than in the CT group (79.7% lower) at week 1, and remained constant until week 4. Hepatic taurine level and gene expression level of cysteine dioxygenase type 1, the rate-limiting enzyme for taurine biosynthesis, were also significantly lower in the LP group than in the CT group (81.1% and 32.5% lower, respectively). Urinary trimethylamine N-oxide (TMAO) levels were significantly higher in the LP group than in the CT group (49.7% higher) at week 2, and remained constant until week 4. Hepatic TMAO level was also higher in the LP group than in the CT group (81.2% higher). Hepatic gene expression levels of flavin-containing monooxygenase 1 and 5, the enzymes for TMAO biosynthesis, were also significantly higher in the LP group than in the CT group (61.6% and 311.8% higher, respectively).CONCLUSIONS: Urinary taurine and TMAO levels substantially respond to LP diet ingestion, and may act as non-invasive biomarker candidates to detect protein undernutrition.

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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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