Your browser doesn't support javascript.
loading
Genetically determined folate deficiency is associated with abnormal hepatic folate profiles in the spontaneously hypertensive rat.
Pravenec, M; Leung, K Y; Zídek, V; Mlejnek, P; Simáková, M; Silhavý, J; Kozich, V; Greene, N D E.
Affiliation
  • Pravenec M; Institute of Physiology of the Czech Academy of Sciences, Prague 4, Czech Republic. pravenec@biomed.cas.cz or UCL Great Ormond Street Institute of Child Health, Guilford Street, London, UK. n.greene@ucl.ac.uk.
Physiol Res ; 67(3): 417-422, 2018 07 17.
Article in En | MEDLINE | ID: mdl-30036071
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<0.01) and 5mTHF monoglutamate was the predominant form in both strains (>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.
Subject(s)
Search on Google
Collection: 01-internacional Database: MEDLINE Main subject: Rats, Inbred SHR / Folate Receptor 1 / Folic Acid / Folic Acid Deficiency / Liver Type of study: Risk_factors_studies Limits: Animals Language: En Journal: Physiol Res Journal subject: FISIOLOGIA Year: 2018 Document type: Article Country of publication:
Search on Google
Collection: 01-internacional Database: MEDLINE Main subject: Rats, Inbred SHR / Folate Receptor 1 / Folic Acid / Folic Acid Deficiency / Liver Type of study: Risk_factors_studies Limits: Animals Language: En Journal: Physiol Res Journal subject: FISIOLOGIA Year: 2018 Document type: Article Country of publication: