RESUMEN
Vitamin B6 deficiency is associated with cardiovascular disease (CVD). Although plasma biomarkers have been proposed, no studies have yet directly profiled heart tissue, and the mechanisms have to be fully defined. Thus, in order to provide better insight into vitamin B6-deficient effects on cardiac functions, we sought to identify the metabolic profile in heart tissue consequent to change in dietary vitamin B6 levels by applying metabolomics. Heart tissues of rats fed a basal diet containing a marginal vitamin B6-deficient, vitamin B6-recommended or vitamin B6-supplemented level were analyzed by metabolomics analysis. Among over 500 detected metabolites, imidazole metabolites including carnosine, anserine, homocarnosine and histamine exhibited the highest decrease upon vitamin B6 deficiency (>-45%, P<.01), along with their precursors ß-alanine, γ-aminobutyric acid (GABA) and 1-methylhistidine. Ornithine was the only metabolite exhibiting an increased level in the vitamin B6-deficient group. Vitamin B6 deficiency significantly attenuated the activity of heart tissue glutamate decarboxylase (GAD), although there was undetectable activity of aspartate decarboxylase (ADC), suggesting that the involvement of vitamin B6 in imidazole metabolite synthesis occurs partly through GABA production by regulating GAD rather than through a straightforward ß-alanine production pathway via ADC in the heart. Notably, vitamin B6 deficiency significantly attenuated citric acid cycle metabolite levels, suggesting cardiac energy metabolism impairment. This study provides a new link between vitamin B6 and cardiac functions, in which marginal vitamin B6 deficiency impairs imidazole and energy metabolism in heart. This newly revealed cardiac metabolic profile may reveal novel molecular targets or foodstuffs for CVD prevention.
