Novel metabolic disturbances in marginal vitamin B₆-deficient rat heart

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 β-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 β-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.