Vitamin B6 deficiency produces metabolic alterations in Drosophila

Introduction: Pyridoxal 5’-phosphate (PLP), the biologically active form of vitamin B6 is involved in 4% of cellular enzymatic activities and its deficiency is responsible for or contributes to several human diseases. The study of underlying mechanisms is still in its infancy and requires suitable model organisms. In Drosophila the deficiency of vitamin B6 produces chromosome aberrations and hallmarks of human diseases including diabetes and cancer. However, the effects of vitamin B6 deficiency have never been examined at a metabolic level. Objectives: This study evaluates the metabolic changes in vitamin B6 deficient Drosophila larvae with the aim of validating flies as a suitable model for diseases associated to vitamin B6 deficiency. Methods: To induce vitamin B6 deficiency we fed Drosophila wild type larvae with 4-deoxypyridoxine (4DP), a PLP antagonist. By HPLC analysis we verified that the 4DP treatment was effective in inducing vitamin B6 deficiency. Using an NMR-based metabolomic approach we compared the metabolites in larval extracts from untreated and 4DP-fed larvae. Results: The NMR spectra analysis identified quantitative differences for sixteen metabolites out of forty, including branched chain and aromatic amino acids, glucose, and lipids, thus revealing interesting possible associations with the phenotypes showed by vitamin B6 deficient flies. Conclusions: Our results validate Drosophila as a suitable model to study in depth the molecular mechanisms underlying human diseases associated with vitamin B6 deficiency and confirmed that 4DP treatment is effective in inducing vitamin B6 deficiency.