Dissecting the role of Folr1 and Folh1 genes in the pathogenesis of metabolic syndrome in spontaneously hypertensive rats

Title:

Dissecting the role of Folr1 and Folh1 genes in the pathogenesis of metabolic syndrome in spontaneously hypertensive rats

Creator:

Šilhavý, J., Jan Krijt, Jitka Sokolová, Václav Zídek, Petr Mlejnek, Miroslava Šimáková, Vojtěch Škop, Trnovská, J., Olena Oliyarnyk, Irena Marková, Hüttl, M., Hana Malínská, Ludmila Kazdová, František Liška, Viktor Kožich, and Michal Pravenec

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:028f95bb-ca47-43e1-b734-b7fbe61f5c49
uuid:028f95bb-ca47-43e1-b734-b7fbe61f5c49
issn:0862-8408

Subject:

foláty, folates, spontaneously hypertensive rat, Folr1 gene, Folh1 gene, cysteine, metabolic syndrome, folate hydrolase, glutamate carboxypeptidase, 14, and 612

Type:

model:article and TEXT

Format:

print, bez média, and svazek

Description:

Increased levels of plasma cysteine predispose to obesity and metabolic disturbances. Our recent genetic analyses in spontaneously hypertensive rats (SHR) revealed mutated Folr1 (folate receptor 1) on chromosome 1 as a quantitative trait gene associated with reduced folate levels, hypercysteinemia and metabolic disturbances. The Folr1 gene is closely linked to the Folh1 (folate hydrolase 1) gene which codes for an enzyme involved in the hydrolysis of dietary polyglutamyl folates in the intestine. In the current study, we obtained evidence that Folh1 mRNA of the BN (Brown Norway) origin is weakly but significantly expressed in the small intestine. Next we analyzed the effects of the Folh1 alleles on folate and sulfur amino acid levels and consecutively on glucose and lipid metabolism using SHR-1 congenic sublines harboring either Folr1 BN and Folh1 SHR alleles or Folr1 SHR and Folh1 BN alleles. Both congenic sublines when compared to SHR controls, exhibited significantly reduced folate clearance and lower plasma cysteine and homocysteine levels which was associated with significantly decreased serum glucose and insulin concentrations and reduced adiposity. These results strongly suggest that, in addition to Folr1 , the Folh1 gene also plays an important role in folate and sulfur amino acid levels and affects glucose and lipid metabolism in the rat., J. Šilhavý, J. Krijt, J. Sokolová, V. Zídek, P. Mlejnek, M. Šimáková, V. Škop, J. Trnovská, O. Oliyarnyk, I. Marková, M. Hüttl, H. Malínská, L. Kazdová, F. Liška, V. Kožich, M. Pravenec., and Obsahuje bibliografii

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Source:

Physiological research | 2018 Volume:67 | Number:4

Harvested from:

CDK

Metadata only:

false