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Expression data from newborn rat skeletal muscle subjected to low protein diet or low protein+taurine during gestation

ABSTRACT: Taurine ameliorates changes occurring in newborn skeletal muscle as a result of gestational protein restriction in C57BL/6 mice, but taurine supplementation effects may be exaggerated in C57BL/6 mice due to their inherent excessive taurinuria. We examined if maternal taurine supplementation could ameliorate changes in gene expression levels, properties of mitochondria, myogenesis, and nutrient transport and sensing, in male newborn skeletal muscle caused by a maternal low protein (LP) diet in Wistar rats. LP diet resulted in an 11% non-significant decrease in birth weight, which was not rescued by taurine supplementation (LP-Tau). LP-Tau offspring had signifi-cantly lower birth weight compared to controls. Gene expression profiling revealed 895 significantly changed genes, mainly an LP-induced down-regulation of genes involved in protein translation. Taurine fully or partially rescued 32% of these changes, but with no distinct pattern as to which genes were rescued. Skeletal muscle taurine content in LP-Tau offspring was increased, but no changes in mRNA levels of the taurine synthesis pathway were observed. Taurine transporter mRNA levels, but not protein levels, were increased by LP diet. Nutrient sensing pathways were largely unaffected in LP or LP-Tau groups, although taurine supplementation caused an unexpected decrease in total Akt and AMPK protein levels. PAT4 amino acid transporter mRNA was increased by LP, and normalized by taurine supplementation. In conclusion, gestational protein restriction in rats decreased genes involved in protein translation in newborn skeletal muscle and led to changes in nutrient transporters. Taurine partly rescued these changes, hence underscoring the im-portance of taurine in development. We used microarrays to detail changes in global programme of gene expression in newborn offspring skeletal muscle brains from rats subjected to either a control diet, a low protein diet or a low protein diet + taurine supplementation

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE89054 | GEO | 2016/10/22

SECONDARY ACCESSION(S): PRJNA350162

REPOSITORIES: GEO

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Project description:In pre-weaning calves, both leucine and threonine play important roles in growth and muscle metabolism. In this study, metabolomics, proteomics and clinical chemistry were used to assess the effects of leucine and threonine supplementation added to milk replacer on 14 newborn Holstein male calves: 7 were fed a control diet (Ctrl) and 7 were fed the Ctrl diet supplemented with 0.3% leucine and 0.3% threonine (LT) from 5.6 days of age to 53.6 days. At this time, blood and semitendinosus muscle biopsies were collected for analysis. Integrated metabolomics and proteomics showed that branched-chain amino acids (BCAA) degradation and mitochondrial oxidative metabolism (citrate cycle and respiratory chain) were the main activated pathways in muscle because of the supplementation. BCAA derivatives and metabolites related to lipid mobilization showed the major changes. The deleterious effects of activated oxidative phosphorylation were balanced by the upregulation of antioxidant proteins. An increase in protein synthesis was indicated by elevated aminoacyl-tRNA biosynthesis and increased S6 ribosomal protein phosphorylation in skeletal muscle. In conclusion, LT group showed greater BCAA availability and mitochondrial oxidative activity; as the muscle cells undergo greater aerobic metabolism, antioxidant defenses were activated to compensate for possible cell damage. Data are available via ProteomeXchange (PXD016098).SIGNIFICANCE: Leucine and threonine are essential amino acids for the pre-weaning calf, being of high importance for growth. In this study, we found that leucine and threonine supplementation of milk replacer to feed pre-weaning calves led to differences in the proteome, metabolome and clinical chemistry analytes in skeletal muscle and plasma, albeit no differences in productive performance were recorded. This study extends our understanding on the metabolism in dairy calves and helps optimizing their nutritional status. Data availability:The proteomics data have been deposited into the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier <a href='https://www.ebi.ac.uk/pride/archive/projects/PXD016098' rel='noopener noreferrer' target='_blank'>PXD016098</a>.

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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Expression data from newborn rat skeletal muscle subjected to low protein diet or low protein+taurine during gestation

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