Dietary Folic Acid Alters Metabolism of Multiple Vitamins in a CerS6- and Sex-Dependent Manner

Folic acid, an oxidized synthetic pro-vitamin B9, is widely used in vitamin supplement formulations and food fortification to maintain optimal folate status in humans. Studies on folic acid (FA) efficiency in improving folate status and correcting folate deficiency pathologies are abundant, but prec...

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Autores principales:	Keri Barron, Besim Ogretmen, Natalia Krupenko
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	dietary folic acid vitamins metabolism nutrients interactions ceramide synthase 6 sex differences Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/164c95a2684849cfac1b447e30895ae4
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spelling	oai:doaj.org-article:164c95a2684849cfac1b447e30895ae42021-11-05T14:35:11ZDietary Folic Acid Alters Metabolism of Multiple Vitamins in a CerS6- and Sex-Dependent Manner2296-861X10.3389/fnut.2021.758403https://doaj.org/article/164c95a2684849cfac1b447e30895ae42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnut.2021.758403/fullhttps://doaj.org/toc/2296-861XFolic acid, an oxidized synthetic pro-vitamin B9, is widely used in vitamin supplement formulations and food fortification to maintain optimal folate status in humans. Studies on folic acid (FA) efficiency in improving folate status and correcting folate deficiency pathologies are abundant, but precise knowledge of FA effects on human and animal tissues is not available. In our recent study, 10-week-old wild-type and CerS6 knockout (KO) mice were placed on FA-deficient, control, or FA over-supplemented diet for 4 weeks. Untargeted metabolomics characterization of mouse liver, brain, and testes tissues after the dietary treatment revealed profound effects of FA on the liver metabolome. Here, we present the analysis of dietary FA effects on tissue concentrations of other vitamins in mice. Despite the expectation that identical dietary supply of the vitamins (excluding FA) to each group should support similar tissue vitamins concentrations, metabolomics data demonstrate significant alterations of tissue concentrations of multiple vitamins by different levels of FA supplementation that were sex- and genotype-dependent. Moreover, we found significant differences in the liver concentration of retinol, thiamin diphosphate, pantetheine, pyridoxal, and pyridoxamine between males and females. While the liver had more changes in vitamins and vitamin derivative levels, the brain tissue and testes also showed changes linked to FA supplementation. Over-supplementation with FA had negative effects on concentrations of vitamins A, B1, B2, and B6, or their metabolites in the liver, but increased intermediates in coenzyme A (CoA) biosynthesis, as well as gamma/beta-tocopherol and phosphorylated forms of B6 in the CerS6 KO brain. Overall, our data demonstrate that dietary FA supplementation significantly affects the metabolism of other vitamins, and that these effects depend on the CerS6 status and sex of the animal. Further research is required to determine whether the observed effects are specific to FA, and the mechanisms that are involved.Keri BarronBesim OgretmenNatalia KrupenkoNatalia KrupenkoFrontiers Media S.A.articledietary folic acidvitaminsmetabolismnutrients interactionsceramide synthase 6sex differencesNutrition. Foods and food supplyTX341-641ENFrontiers in Nutrition, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dietary folic acid vitamins metabolism nutrients interactions ceramide synthase 6 sex differences Nutrition. Foods and food supply TX341-641
spellingShingle	dietary folic acid vitamins metabolism nutrients interactions ceramide synthase 6 sex differences Nutrition. Foods and food supply TX341-641 Keri Barron Besim Ogretmen Natalia Krupenko Natalia Krupenko Dietary Folic Acid Alters Metabolism of Multiple Vitamins in a CerS6- and Sex-Dependent Manner
description	Folic acid, an oxidized synthetic pro-vitamin B9, is widely used in vitamin supplement formulations and food fortification to maintain optimal folate status in humans. Studies on folic acid (FA) efficiency in improving folate status and correcting folate deficiency pathologies are abundant, but precise knowledge of FA effects on human and animal tissues is not available. In our recent study, 10-week-old wild-type and CerS6 knockout (KO) mice were placed on FA-deficient, control, or FA over-supplemented diet for 4 weeks. Untargeted metabolomics characterization of mouse liver, brain, and testes tissues after the dietary treatment revealed profound effects of FA on the liver metabolome. Here, we present the analysis of dietary FA effects on tissue concentrations of other vitamins in mice. Despite the expectation that identical dietary supply of the vitamins (excluding FA) to each group should support similar tissue vitamins concentrations, metabolomics data demonstrate significant alterations of tissue concentrations of multiple vitamins by different levels of FA supplementation that were sex- and genotype-dependent. Moreover, we found significant differences in the liver concentration of retinol, thiamin diphosphate, pantetheine, pyridoxal, and pyridoxamine between males and females. While the liver had more changes in vitamins and vitamin derivative levels, the brain tissue and testes also showed changes linked to FA supplementation. Over-supplementation with FA had negative effects on concentrations of vitamins A, B1, B2, and B6, or their metabolites in the liver, but increased intermediates in coenzyme A (CoA) biosynthesis, as well as gamma/beta-tocopherol and phosphorylated forms of B6 in the CerS6 KO brain. Overall, our data demonstrate that dietary FA supplementation significantly affects the metabolism of other vitamins, and that these effects depend on the CerS6 status and sex of the animal. Further research is required to determine whether the observed effects are specific to FA, and the mechanisms that are involved.
format	article
author	Keri Barron Besim Ogretmen Natalia Krupenko Natalia Krupenko
author_facet	Keri Barron Besim Ogretmen Natalia Krupenko Natalia Krupenko
author_sort	Keri Barron
title	Dietary Folic Acid Alters Metabolism of Multiple Vitamins in a CerS6- and Sex-Dependent Manner
title_short	Dietary Folic Acid Alters Metabolism of Multiple Vitamins in a CerS6- and Sex-Dependent Manner
title_full	Dietary Folic Acid Alters Metabolism of Multiple Vitamins in a CerS6- and Sex-Dependent Manner
title_fullStr	Dietary Folic Acid Alters Metabolism of Multiple Vitamins in a CerS6- and Sex-Dependent Manner
title_full_unstemmed	Dietary Folic Acid Alters Metabolism of Multiple Vitamins in a CerS6- and Sex-Dependent Manner
title_sort	dietary folic acid alters metabolism of multiple vitamins in a cers6- and sex-dependent manner
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/164c95a2684849cfac1b447e30895ae4
work_keys_str_mv	AT keribarron dietaryfolicacidaltersmetabolismofmultiplevitaminsinacers6andsexdependentmanner AT besimogretmen dietaryfolicacidaltersmetabolismofmultiplevitaminsinacers6andsexdependentmanner AT nataliakrupenko dietaryfolicacidaltersmetabolismofmultiplevitaminsinacers6andsexdependentmanner AT nataliakrupenko dietaryfolicacidaltersmetabolismofmultiplevitaminsinacers6andsexdependentmanner
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Dietary Folic Acid Alters Metabolism of Multiple Vitamins in a CerS6- and Sex-Dependent Manner

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