期刊
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
卷 65, 期 -, 页码 26-34出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2018.11.004
关键词
Vitamin B-6 deficiency; Imidazole dipeptide; Carnosine; Glutamate decarboxylase; Energy metabolism; Heart disease
资金
- Funds for the Development of Human Resources in Science and Technology under the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, through the Home for Innovative Researchers and Academic Knowledge Users (HIRAKU) consortium, Hir
Vitamin B-6 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-6-deficient effects on cardiac functions, we sought to identify the metabolic profile in heart tissue consequent to change in dietary vitamin B-6 levels by applying metabolomics. Heart tissues of rats fed a basal diet containing a marginal vitamin B-6-deficient, vitamin B-6 -recommended or vitamin B-6-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-6 deficiency (>-45%, P<.01), along with their precursors beta-alanine, gamma-aminobutyric acid (GABA) and 1-methylhistidine. Ornithine was the only metabolite exhibiting an increased level in the vitamin B-6-deficient group. Vitamin B-6 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-6 in imidazole metabolite synthesis occurs partly through GABA production by regulating GAD rather than through a straightforward beta-alanine production pathway via ADC in the heart. Notably, vitamin B-6 deficiency significantly attenuated citric acid cycle metabolite levels, suggesting cardiac energy metabolism impairment. This study provides a new link between vitamin B-6 and cardiac functions, in which marginal vitamin B-6 deficiency impairs imidazole and energy metabolism in heart. This newly revealed cardiac metabolic profile may reveal novel molecular targets or foodstuffs for CVD prevention. (C) 2018 Elsevier Inc. All rights reserved.
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