Novel metabolic disturbances in marginal vitamin B-deficient rat heart.

J Nutr Biochem

Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan; Division of Food Science and Biofunctions, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan.

Published: March 2019

Vitamin B 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 B-deficient effects on cardiac functions, we sought to identify the metabolic profile in heart tissue consequent to change in dietary vitamin B levels by applying metabolomics. Heart tissues of rats fed a basal diet containing a marginal vitamin B-deficient, vitamin B-recommended or vitamin B-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 B 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 B-deficient group. Vitamin B 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 B 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 B deficiency significantly attenuated citric acid cycle metabolite levels, suggesting cardiac energy metabolism impairment. This study provides a new link between vitamin B and cardiac functions, in which marginal vitamin B deficiency impairs imidazole and energy metabolism in heart. This newly revealed cardiac metabolic profile may reveal novel molecular targets or foodstuffs for CVD prevention.

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http://dx.doi.org/10.1016/j.jnutbio.2018.11.004DOI Listing

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