scholarly journals Downregulation of the Glo1 Gene Is Associated with Reduced Adiposity and Ectopic Fat Accumulation in Spontaneously Hypertensive Rats

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1179
Author(s):  
Jan Šilhavý ◽  
Hana Malínská ◽  
Martina Hüttl ◽  
Irena Marková ◽  
Olena Oliyarnyk ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Serum Insulin ◽  
Relative Weight ◽  
Ectopic Fat ◽  
Hypertensive Rats ◽  
Serum Triglycerides ◽  
Fat Accumulation ◽  
Spontaneously Hypertensive ◽  
Glucose And Lipid Metabolism ◽  
Tissue Lipids

Methylglyoxal (MG), a potent precursor of advanced glycation end-products (AGE), is increased in metabolic disorders such as diabetes and obesity. MG and other dicarbonyl metabolites are detoxified by the glyoxalase system in which glyoxalase 1, coded by the Glo1 gene, serves as the rate-limiting enzyme. In this study, we analyzed the effects of Glo1 downregulation on glucose and lipid metabolism parameters in spontaneously hypertensive rats (SHR) by targeting the Glo1 gene (SHR-Glo1+/− heterozygotes). Compared to SHR wild-type animals, SHR-Glo1+/− rats showed significantly reduced Glo1 expression and lower GLO1 activity in tissues associated with increased MG levels. In contrast to SHR controls, SHR-Glo1+/− rats exhibited lower relative weight of epididymal fat, reduced ectopic fat accumulation in the liver and heart, and decreased serum triglycerides. In addition, compared to controls, SHR-Glo1+/− rats showed reduced serum insulin and increased basal and insulin stimulated incorporation of glucose into white adipose tissue lipids (lipogenesis). Reduced ectopic fat accumulation in the heart was associated with significantly increased pAMPK/AMPK ratio and GLUT4 activity. These results provide evidence that Glo1 downregulation in SHR is associated with reduced adiposity and ectopic fat accumulation, most likely mediated by AMPK activation in the heart.

scholarly journals 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

2007 ◽  
Vol 97 (1) ◽  
pp. 67-76 ◽  
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.

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

2018 ◽  
pp. 657-662 ◽  
Author(s):  
J. ŠILHAVÝ ◽  
J. KRIJT ◽  
J. SOKOLOVÁ ◽  
V. ZÍDEK ◽  
P. MLEJNEK ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Amino Acid ◽  
Spontaneously Hypertensive Rats ◽  
Brown Norway ◽  
Sulfur Amino Acid ◽  
Hypertensive Rats ◽  
Metabolic Disturbances ◽  
Spontaneously Hypertensive ◽  
Glucose And Lipid Metabolism ◽  
Amino Acid Levels

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.

scholarly journals Hepatotoxic Effects of Fenofibrate in Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

2016 ◽  
pp. 891-899 ◽  
Author(s):  
V. ŠKOP ◽  
J. TRNOVSKÁ ◽  
O. OLIYARNYK ◽  
I. MARKOVÁ ◽  
H. MALÍNSKÁ ◽  
...  
Keyword(s):  
Body Weight ◽  
Spontaneously Hypertensive Rats ◽  
Hdl Cholesterol ◽  
Metabolic Effects ◽  
C Reactive Protein ◽  
Hypertensive Rats ◽  
Serum Triglycerides ◽  
Spontaneously Hypertensive ◽  
Reactive Protein ◽  
Anti Inflammatory

Dyslipidemia and inflammation play an important role in the pathogenesis of cardiovascular and liver disease. Fenofibrate has a well-known efficacy to reduce cholesterol and triglycerides. Combination with statins can ameliorate hypolipidemic and anti-inflammatory effects of fibrates. In the current study, we tested the anti-inflammatory and metabolic effects of fenofibrate alone and in combination with rosuvastatin in a model of inflammation and metabolic syndrome, using spontaneously hypertensive rats expressing the human C-reactive protein transgene (SHR-CRP transgenic rats). SHR-CRP rats treated with fenofibrate alone (100 mg/kg body weight) or in combination with rosuvastatin (20 mg/kg body weight) vs. SHR-CRP untreated controls showed increased levels of proinflammatory marker IL6, increased concentrations of ALT, AST and ALP, increased oxidative stress in the liver and necrotic changes of the liver. In addition, SHR-CRP rats treated with fenofibrate, or with fenofibrate combined with rosuvastatin vs. untreated controls, exhibited increased serum triglycerides and reduced HDL cholesterol, as well as reduced hepatic triglyceride, cholesterol and glycogen concentrations. These findings suggest that in the presence of high levels of human CRP, fenofibrate can induce liver damage even in combination with rosuvastatin. Accordingly, these results caution against the possible hepatotoxic effects of fenofibrate in patients with high levels of CRP.

scholarly journals Sterol Regulatory Element Binding Protein 2 Overexpression Is Associated With Reduced Adipogenesis and Ectopic Fat Accumulation in Transgenic Spontaneously Hypertensive Rats

2014 ◽  
pp. 587-590 ◽  
Author(s):  
V. LANDA ◽  
V. ZÍDEK ◽  
P. MLEJNEK ◽  
M. ŠIMÁKOVÁ ◽  
J. ŠILHAVÝ ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Binding Protein ◽  
Regulatory Element ◽  
Relative Weight ◽  
Ectopic Fat ◽  
Transgenic Rats ◽  
Fat Accumulation ◽  
Spontaneously Hypertensive ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

It has been reported that the major function of the sterol regulatory element binding protein 2 (SREBP-2) is to activate preferentially cholesterol biosynthesis in liver and adipose tissue rather than fatty acid synthesis. In the current study, we analyzed the effects of overexpression of human dominant-positive SREBP-2 transgene under control of PEPCK promoter in the spontaneously hypertensive rat (SHR) on lipid and glucose metabolism. Transgenic overexpression of SREBP-2 was associated with significantly higher hepatic triglycerides (20.4±0.9 vs. 17.0±0.05 µmol/g, P<0.05) but not cholesterol (10.6±0.4 vs. 10.9±0.4 µmol/g) and decreased relative weight of epididymal fat pad (0.73±0.03 vs. 0.830.03, P<0.05). In addition, muscle triglyceride (15.8±3.7 vs. 8.5±1.2 µmol/g, P<0.001) and cholesterol (3.6±0.5 vs. 2.1±0.1 µmol/g, P<0.05) concentrations were significantly increased in transgenic rats when compared to SHR controls. Ectopic fat accumulation was associated with significantly increased serum glucose levels (6.4±0.1 vs. 5.9±0.1 mmol/l, P<0.005) and reduced insulin levels (1.78±0.33 vs. 2.73±0.37 nmol/l, P<0.05) in transgenic rats. These results provide evidence for important role of SREBP-2 in regulation of lipid and glucose metabolism.

scholarly journals Rosuvastatin Ameliorates Inflammation, Renal Fat Accumulation, and Kidney Injury in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

2015 ◽  
pp. 295-301 ◽  
Author(s):  
J. ŠILHAVÝ ◽  
V. ZÍDEK ◽  
V. LANDA ◽  
M. ŠIMÁKOVÁ ◽  
P. MLEJNEK ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Kidney Injury ◽  
Organ Injury ◽  
Hypertensive Rats ◽  
Transgenic Rats ◽  
Fat Accumulation ◽  
Transgenic Expression ◽  
Spontaneously Hypertensive ◽  
Cardiac Inflammation ◽  
Reactive Protein

Recently, we derived “humanized” spontaneously hypertensive rats (SHR-CRP) in which transgenic expression of human CRP induces inflammation, oxidative stress, several features of metabolic syndrome and target organ injury. In addition, we found that rosuvastatin treatment of SHR-CRP transgenic rats can protect against pro-inflammatory effects of human CRP and also reduce cardiac inflammation and oxidative damage. In the current study, we tested the effects of rosuvastatin (5 mg/kg) on kidney injury in SHR-CRP males versus untreated SHR-CRP and SHR controls. All rats were fed a high sucrose diet. In SHR-CRP transgenic rats, treatment with rosuvastatin for 10 weeks, compared to untreated transgenic rats and SHR controls, was associated with significantly reduced systemic inflammation which was accompanied with activation of antioxidative enzymes in the kidney, lower renal fat accumulation, and with amelioration of histopathological changes in the kidney. These findings provide evidence that, in the presence of high CRP levels, rosuvastatin exhibits significant anti-inflammatory, anti-oxidative, and renoprotective effects.

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