Dissecting the Role of Folr1 and Folh1 Genes in the Pathogenesis of Metabolic Syndrome in Spontaneously Hypertensive Rats

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.

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General Survey of Glucose and Lipid Metabolism in Spontaneously Hypertensive Rats (SHR)

Japanese Heart Journal ◽

10.1536/ihj.14.159 ◽

1973 ◽

Vol 14 (2) ◽

pp. 159-159 ◽

Cited By ~ 1

Author(s):

Kiro SHIMAMOTO ◽

Akio TERAOKA ◽

Hisashi IWATSUKA ◽

Ziro SUZUOKI

Keyword(s):

Lipid Metabolism ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

General Survey ◽

Spontaneously Hypertensive ◽

Glucose And Lipid Metabolism

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The Driselase-treated fraction of rice bran is a more effective dietary factor to improve hypertension, glucose and lipid metabolism in stroke-prone spontaneously hypertensive rats compared to ferulic acid

British Journal Of Nutrition ◽

10.1017/s000711450721013x ◽

2007 ◽

Vol 97 (1) ◽

pp. 67-76 ◽

Cited By ~ 21

Author(s):

Ardiansyah ◽

Hitoshi Shirakawa ◽

Takuya Koseki ◽

Katsumi Hashizume ◽

Michio Komai

Keyword(s):

Lipid Metabolism ◽

Ferulic Acid ◽

Rice Bran ◽

Spontaneously Hypertensive Rats ◽

Control Diet ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Glucose And Lipid Metabolism ◽

The Metabolic Syndrome ◽

Hepatic Triacylglycerol

The aim of this study is to investigate the effects of dietary supplementation with the Driselase-treated fraction (DF) of rice bran and ferulic acid (FA) on hypertension and glucose and lipid metabolism in stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP at 4 weeks of age were divided into three groups, and for 8 weeks were fed (1) a control diet based on AIN-93M, (2) a DF of rice bran-supplemented diet at 60 g/kg and (3) an FA-supplemented diet at 0·01 g/kg. Means and standard errors were calculated and the data were tested by one-way ANOVA followed by a least significance difference test. The results showed that both the DF and FA diets significantly improved hypertension as well as glucose tolerance, plasma nitric oxide (NOx), urinary 8-hydroxy-2′-deoxyguanosine and other parameters. In particular, compared to the FA diet, the DF diet produced a significant improvement in urinary NOx, hepatic triacylglycerol and several mRNA expressions of metabolic parameters involved in glucose and lipid metabolisms. The results of the metabolic syndrome-related parameters obtained from this study suggest that the DF diet is more effective than the FA diet.

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