Genetically Determined Folate Deficiency Is Associated With Abnormal Hepatic Folate Profiles in the Spontaneously Hypertensive Rat

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10377514" target="_blank" >RIV/00216208:11110/18:10377514 - isvavai.cz</a>

Alternative codes found

RIV/67985823:_____/18:00492454 RIV/00064165:_____/18:10377514

Result on the web

<a href="http://www.biomed.cas.cz/physiolres/pdf/67/67_417.pdf" target="_blank" >http://www.biomed.cas.cz/physiolres/pdf/67/67_417.pdf</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Genetically Determined Folate Deficiency Is Associated With Abnormal Hepatic Folate Profiles in the Spontaneously Hypertensive Rat

Original language description

Increased levels of plasma cysteine are associated with obesity and metabolic disturbances. Our recent genetic analyses in spontaneously hypertensive rats (SHR) revealed a mutated Folr1 (folate receptor 1) as the quantitative trait gene associated with diminished renal Folr1 expression, lower plasma folate levels, hypercysteinemia, hyperhomocysteinemia and metabolic disturbances. To further analyse the effects of the Folr1 gene expression on folate metabolism, we used mass spectrometry to quantify folate profiles in the plasma and liver of an SHR-1 congenic strain, with wild type Folr1 allele on the SHR genetic background, and compared them with the SHR strain. In the plasma, concentration of 5-methyltetrahydrofolate (5mTHF) was significantly higher in SHR-1 congenic rats compared to SHR (60+-6 vs. 42+-2 nmol/l, P&lt;0.01) and 5mTHF monoglutamate was the predominant form in both strains (&gt;99 % of total folate). In the liver, SHR-1 congenic rats showed a significantly increased level of 5mTHF and decreased concentrations of dihydrofolate (DHF), tetrahydrofolate (THF) and formyl-THF when compared to the SHR strain. We also analysed the extent of folate glutamylation in the liver. Compared with the SHR strain, congenic wild-type Folr1 rats had significantly higher levels of 5mTHF monoglutamate. On the other hand, 5mTHF penta- and hexaglutamates were significantly higher in SHR when compared to SHR-1 rats. This inverse relationship of rat hepatic folate polyglutamate chain length and folate sufficiency was also true for other folate species. These results strongly indicate that the whole body homeostasis of folates is substantially impaired in SHR rats compared to the SHR-1 congenic strain and might be contributing to the associated metabolic disturbances observed in our previous studies.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10600 - Biological sciences

Project

<a href="/en/project/GA14-09283S" target="_blank" >GA14-09283S: Dissecting the role of renal folate metabolism in blood pressure regulation in spontaneously hypertensive rats</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Physiological Research

ISSN

0862-8408

e-ISSN

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Volume of the periodical

67

Issue of the periodical within the volume

3

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

6

Pages from-to

417-422

UT code for WoS article

000439466000006

EID of the result in the Scopus database

2-s2.0-85050367705