Abstract
Purpose
Vitamin B6 status in the body is affected by several factors including dietary supply of the antivitamin B6 factor, 1-amino d-proline (1ADP), which is present in flaxseed. Owing to the prevalence of moderate B6 deficiency in the general population, a co-occurrence of 1ADP may lead to a further deterioration of B6 status. To this end, we applied a nontargeted metabolomics approach to identify potential plasma lipophilic biomarkers of deleterious effect of 1ADP on moderately vitamin B6-deficient rats using a high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.
Methods
Twenty-four rats were fed with a semi-purified diet containing pyridoxine·HCl (PN·HCl) either 7 mg/kg diet (optimal B6) or 0.7 mg/kg diet (moderate B6). The rats were divided into four treatments (n = 6), and one treatment in each B6 diet group was also fed ad libitum with 10 mg/kg diet of synthetic 1ADP. After 5 weeks of study, plasma was collected from the rats and lipophilic metabolites were extracted using acetonitrile as a solvent for analysis.
Results
Ten potential plasma lipophilic biomarkers were identified out of >2500 detected entities, which showed significant differences between the treatments. Plasma glycocholic acid, glycoursodeoxycholic acid, murocholic acid, N-docosahexaenoyl GABA, N-arachidonoyl GABA, lumula, nandrolone and orthothymotinic acid concentrations were significantly elevated, while plasma cystamine and 3-methyleneoxindole concentrations were significantly reduced as a result of either low B6 status or 1ADP or their interaction.
Conclusion
Changes in these metabolites revealed a potential defect in pathways linked with the biosynthesis and metabolism of bile acid components, N-acyl amino acids, analgesic androgens, anti-inflammatory and neuroprotective molecules. We also noted that the changes in these biomarkers can be alleviated by the application of adequate vitamin B6.
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Abbreviations
- 1ADP:
-
1-Amino d-proline
- ASBT:
-
Apical sodium-dependent bile acid transporter
- Ar-EA:
-
N-Arachidonoyl ethanolamide
- CYP:
-
Cytochrome P450
- FAAH:
-
Fatty acid amide hydrolase
- FXR:
-
Farnesoid X receptor
- HPLC–QTOF-MS:
-
High-performance liquid chromatography/quadrupole time-of-flight mass spectrometry
- NAGABA:
-
N-Arachidonoyl γ-butyric acid
- NDGABA:
-
N-Docosahexaenoyl γ-aminobutyric acid
- NTCP:
-
Sodium taurocholate co-transporting polypeptide
- OATP:
-
Organic anion transporting polypeptide
- OST:
-
Solute transporters
- PLP:
-
Pyridoxal 5′-phosphate
- PN·HCl:
-
Pyridoxine·hydrochloride
- SULT:
-
Sulfotransferase
- UGT:
-
UDP-glucuronosyltransferase
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Acknowledgments
This study was supported by Discovery Grants Program of the Natural Sciences and Engineering Research Council of Canada (NSERC; JDH and MA). Shyamchand Mayengbam was the recipient of a NSERC CREATE. J.D.H., S.M. and M.A. designed research; S.M. conducted research; S.M. and M.A. analyzed data; S.M. wrote the manuscript; J.D.H. and M.A. reviewed manuscript, and M.A. had primary responsibility for the final content. All authors read and approved the final manuscript.
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Authors of this study declare no conflict of interests.
Ethical standard
The animal study was conducted according to the procedures approved by Animal User and Animal Care Committees, University of Manitoba and adhered to the guidelines of Canadian Council of Animal Care.
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Mayengbam, S., House, J.D. & Aliani, M. Investigation of vitamin B6 inadequacy, induced by exposure to the anti-B6 factor 1-amino d-proline, on plasma lipophilic metabolites of rats: a metabolomics approach. Eur J Nutr 55, 1213–1223 (2016). https://doi.org/10.1007/s00394-015-0934-x
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DOI: https://doi.org/10.1007/s00394-015-0934-x