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The Effects of Folate Deficiency and Folic Acid Supplementation on Folate Absorption and Metabolism in a Mouse Model
Author(s) -
Warzyszynska Joanna,
Im David,
Bloemen Nicolaas,
Sohn KyoungJin,
Kim SungEun,
Zuchniak Anna,
Aufreiter Susanne,
O'Connor Deborah,
Kim YoungIn
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.919.17
Subject(s) - methylenetetrahydrofolate reductase , serine hydroxymethyltransferase , endocrinology , medicine , dihydrofolate reductase , metabolism , folate receptor , biology , antifolate , gene expression , thymidylate synthase , chemistry , biochemistry , enzyme , serine , antimetabolite , methotrexate , gene , allele , fluorouracil , cancer , cancer cell
The effects of folate deficiency and folic acid (FA) supplementation on folate absorption and metabolism have not been well established in vivo . We investigated the effects of folate deficiency and FA supplementation on gene expression of folate receptors/transporters and metabolic enzymes in a mouse model. Postweaning C57BL/6 mice were randomized to receive diets containing 0 (moderate folate deficiency), 2 (control) or 20 mg FA/kg of diet for 3 months. Gene expression was assessed by real‐time RT‐qPCR. Plasma folate and unmetabolized FA and hepatic and small intestinal folate concentrations accurately reflected the supplemental levels of FA ( p ‐trend<0.0001). Expression of the proton‐coupled folate transporter ( Pcft ), reduced folate carrier ( Rfc ) and folate receptor‐1 ( Folr1 ) in the small intestine and Folr1 in the liver was inversely associated with the supplemental levels of FA ( p‐ trend<0.0001). The supplemental levels of FA were inversely associated with thymidylate synthase ( Tyms ) expression in the liver and serine hydroxymethyltransferase ( Shmt1 ) expression in the small intestine ( p ‐trend<0.05) but were not associated with the expression of dihydrofolate reductase ( Dhfr ) or methylenetetrahydrofolate reductase ( Mthfr ) in either tissue. Our data suggest that folate deficiency and FA supplementation modulate expression of genes involved in folate absorption and metabolism, likely as a homeostatic mechanism. However, FA supplementation may also adversely influence folate absorption and metabolism by dysregulation of these pathways. Supported by CIHR MOP#106446