Pathophysiological, Genetic and Gene Expression Features of a Novel Rodent Model of the Cardio-Metabolic Syndrome

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) can exert opposed effects depending on the dosage: low levels can be involved in signalling and adaptive processes, while higher levels can exert deleterious effects in cells and tissues. Our aim was to emulate a chronic ex vivo oxidative stress situation through a 2 h exposure of immune cells to sustained H2O2 produced by glucose oxidase (GOX), at high or low production rate, in order to determine dissimilar responses of peripheral blood mononuclear cells (PBMCs) and neutrophils on ROS and cytokine production, and mitochondrial dynamics-related proteins, pro/anti-inflammatory and anti-oxidant gene expression. Immune cells were obtained from subjects with metabolic syndrome. H2O2 at low concentrations can trigger a transient anti-inflammatory adiponectin secretion and reduced gene expression of toll-like receptors (TLRs) in PBMCs but may act as a stimulator of proinflammatory genes (IL6, IL8) and mitochondrial dynamics-related proteins (Mtf2, NRF2, Tfam). H2O2 at a high concentration enhances the expression of pro-inflammatory genes (TLR2 and IL1β) and diminishes the expression of mitochondrial dynamics-related proteins (Mtf1, Tfam) and antioxidant enzymes (Cu/Zn SOD) in PBMCs. The GOX treatments produce dissimilar changes in immune cells: Neutrophils were more resistant to H2O2 effects and exhibited a more constant response in terms of gene expression than PBMCs. We observe emerging roles of H2O2 in mitochondrial dynamics and redox and inflammation processes in immune cells.

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Cholesterol Transporters ABCA1 and ABCG1 Gene Expression in Peripheral Blood Mononuclear Cells in Patients with Metabolic Syndrome

Cholesterol ◽

10.1155/2015/682904 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 12

Author(s):

Zahra Tavoosi ◽

Hemen Moradi-Sardareh ◽

Massoud Saidijam ◽

Reza Yadegarazari ◽

Shiva Borzuei ◽

...

Keyword(s):

Gene Expression ◽

Metabolic Syndrome ◽

Mononuclear Cells ◽

Fasting Blood Glucose ◽

Control Group ◽

Regulation Mechanism ◽

Healthy Individuals ◽

Peripheral Blood Mononuclear ◽

Significant Difference ◽

Abca1 Expression

ABCA1 and ABCG1 genes encode the cholesterol transporter proteins that play a key role in cholesterol and phospholipids homeostasis. This study was aimed at evaluating and comparing ABCA1 and ABCG1 genes expression in metabolic syndrome patients and healthy individuals. This case-control study was performed on 36 patients with metabolic syndrome and the same number of healthy individuals in Hamadan (west of Iran) during 2013-2014. Total RNA was extracted from mononuclear cells and purified using RNeasy Mini Kit column. The expression of ABCA1 and ABCG1 genes was performed by qRT-PCR. Lipid profile and fasting blood glucose were measured using colorimetric procedures. ABCG1 expression in metabolic syndrome patients was significantly lower (about 75%) compared to that of control group, while for ABCA1 expression, there was no significant difference between the two studied groups. Comparison of other parameters such as HDL-C, FBS, BMI, waist circumference, and systolic and diastolic blood pressure between metabolic syndrome patients and healthy individuals showed significant differences (P<0.05). Decrease in ABCG1 expression in metabolic syndrome patients compared to healthy individuals suggests that hyperglycemia, related metabolites, and hyperlipidemia over the transporter capacity resulted in decreased expression of ABCG1. Absence of a significant change in ABCA1 gene expression between two groups can indicate a different regulation mechanism for ABCA1 expression.

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Improvement of Cardiac Fibrosis Biomarkers through Inflammation Inhibition by Green Tea and Decaffeinated Light Roasted Green Coffee Extract Combination Administration in Metabolic Syndrome Rat Model

F1000Research ◽

10.12688/f1000research.55468.1 ◽

2021 ◽

Vol 10 ◽

pp. 1013

Author(s):

Mifetika Lukitasari ◽

Mohammad Saifur Rohman ◽

Dwi Adi Nugroho ◽

Nila Aisyah Wahyuni ◽

Mukhamad Nur Kholis ◽

...

Keyword(s):

Gene Expression ◽

Metabolic Syndrome ◽

Green Tea ◽

Rat Model ◽

Cardiac Fibrosis ◽

Significant Risk ◽

Green Coffee ◽

The Metabolic Syndrome ◽

Tnf Α ◽

Tgf Β1

Background: Metabolic syndrome is a significant risk factor for cardiovascular diseases. Green tea and green coffee extracts, antioxidant and anti-inflammatory agents may participate in metabolic syndrome-induced cardiac fibrosis alleviation. However, the effect of combination of those extracts still needs exploration. Therefore, this study investigated the effect of green tea and decaffeinated light roasted green coffee extracts and their combination in metabolic syndrome-induced cardiac fibrosis rats. Methods: Metabolic syndrome rat model was i1nduced through high-fat high sucrose diets feeding for 8 weeks and injection of low dose streptozotocin at the 2nd week. The metabolic syndrome rats were divided into 4 experimental groups metabolic syndrome rats (MS); metabolic syndrome rats treated with 300 mg/ kg b.w green tea extract (GT); metabolic syndrome rats treated with 200 mg/ kg b.w decaffeinated light roasted green coffee extract (GC); metabolic syndrome rats treated with the combination of the two extracts (CE); and a normal control (NC) group was added. Angiotensin 2 level was analyzed by ELISA method. Gene expression of NF-κB, TNF-α, IL-6, Tgf-β1, Rac-1, and α-sma were analyzed by touchdown polymerase chain reaction methods. Results: Metabolic syndrome rats treated with green tea and decaffeinated light roasted green coffee significantly decreased angiotensin-2 serum level and cardiac inflammation and fibrosis gene expression level (NF-κB, TNF-α, IL-6, Tgf-β1, Rac-1, and α-sma). More significant alleviation was observed in the combination group. Conclusion: This study suggested that combination of green tea and decaffeinated light roasted green coffee extracts showed better improvement in metabolic syndrome-induced cardiac fibrosis rat model compared to that of single extract administration through inflammation inhibition

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THE LEPTIN GENE IS A MARKER FOR THE CELL THERAPY OF METABOLIC SYNDROME

Biomeditsina ◽

10.33647/2074-5982-15-3-12-22 ◽

2019 ◽

pp. 12-22

Author(s):

N. V. Petrova

Keyword(s):

Gene Expression ◽

Metabolic Syndrome ◽

Cell Therapy ◽

Bone Marrow Cells ◽

Liver And Pancreas ◽

A Cell ◽

Polymerase Chain ◽

Lep Gene ◽

The Brain

It is shown that the level of the Lep gene expression is a marker for B/Ks-Leprᵈᵇ/+ mice, which line serves as an optimal model for describing metabolic syndrome (MS) in preclinical studies. Mice were transplanted with cultured isogenic bone marrow cells (BMC) from heterozygous db/+ donors. The recipients were divided into two groups according to an early or advanced stage of MS development. We analyzed the expression of the Lep gene on the 3rd, 8th and 14th day following the administration of stem BMCs in the brain, liver and pancreas cells by polymerase chain reaction (PCR) in real time. The Lep gene expression was evaluated in terms of the number of cDNA copies. According to our data, leptin is a complete regulator of metabolic processes due to its effect on the hypothalamus, which, together with the hippocampus, controls the production of acetylcholine and insulin in the brain. We have proven the role of the Lep gene as a quantitative criterion for evaluating the effi cacy of a cell therapy in MS.

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A rodent model of low- to moderate-dose ethanol consumption during pregnancy: patterns of ethanol consumption and effects on fetal and offspring growth

Reproduction Fertility and Development ◽

10.1071/rd11200 ◽

2012 ◽

Vol 24 (6) ◽

pp. 859 ◽

Cited By ~ 26

Author(s):

Megan E. Probyn ◽

Simone Zanini ◽

Leigh C. Ward ◽

John F. Bertram ◽

Karen M. Moritz

Keyword(s):

Gene Expression ◽

Repeated Measures ◽

Ethanol Consumption ◽

Liquid Diet ◽

Rodent Model ◽

Sprague Dawley ◽

Moderate Dose ◽

Crown Rump Length ◽

Dietary Consumption ◽

Offspring Growth

It is unknown whether low to moderate maternal alcohol consumption adversely affects postnatal health. The aim of the present study was to develop a rodent model of low–moderate-dose prenatal ethanol (EtOH) exposure. Sprague-Dawley rats were fed a liquid diet with or without 6% v/v EtOH throughout gestation and the pattern of dietary consumption determined. Fetal bodyweights and hepatic alcohol-metabolising gene expression were measured on embryonic Day (E) 20 and offspring growth studied until 1 year. At E8 the plasma EtOH concentration was 0.03%. There was little difference in dietary consumption between the two treatment groups. At E20, EtOH-exposed fetuses were significantly lighter than controls and had significantly decreased ADH4 and increased CYP2E1 gene expression. Offspring killed on postnatal Day (PN) 30 did not exhibit any growth deficits. Longitudinal repeated measures of offspring growth demonstrated slower growth in males from EtOH-fed dams between 7 and 12 months of age; a cohort of male pups killed at 8 months of age had a reduced crown–rump length and kidney weight. In conclusion, a liquid diet of 6% v/v EtOH fed to pregnant dams throughout gestation caused a 3–8% reduction in fetal growth and brain sparing, with growth differences observed in male offspring later in life. This model will be useful for future studies on the effects of low–moderate EtOH on the developmental origins of health and disease.

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