The intestinal metabolism and DNA binding of benzo[a]pyrene in guinea-pigs fed normal, high-fat and high-cholesterol diets

Recent studies indicate an accelerated progression of nonalcoholic steatohepatitis (NASH) in postmenopausal women. Hypercholesterolemia, an important risk factor for NASH progression, is often observed after menopause. This study examined the effects of estrogen on NASH in ovariectomized (OVX) mice fed a high-fat and high-cholesterol (HFHC) diet. To investigate the effects of estrogen deficiency, OVX mice and sham-operated (SO) mice were fed normal chow or HFHC diet for 6 wk. Next, to investigate the effects of exogenous estrogen replenishment, OVX mice fed with HFHC diet were treated with implanted hormone release pellets (containing 17β-estradiol or placebo vehicle) for 6 wk. OVX mice on the HFHC diet showed enhanced liver injury with increased liver macrophage infiltration and elevated serum cholesterol levels compared with SO-HFHC mice. Hepatocyte monocyte chemoattractant protein-1 (MCP1) protein expression in OVX-HFHC mice was also enhanced compared with SO-HFHC mice. In addition, hepatic inflammatory gene expressions, including monocytes chemokine (C-C motif) receptor 2 (CCR2), were significantly elevated in OVX-HFHC mice. Estrogen treatment improved serum cholesterol levels, liver injury, macrophage infiltration, and inflammatory gene expressions in OVX-HFHC mice. Moreover, the elevated expression of liver CCR2 and MCP1 were decreased by estrogen treatment in OVX-HFHC mice, whereas low-density lipoprotein dose dependently enhanced CCR2 expression in THP1 monocytes. Our study demonstrated that estrogen deficiency accelerated NASH progression in OVX mice fed HFHC diet and that this effect was improved by estrogen therapy. Hypercholesterolemia in postmenopausal women would be a potential risk factor for NASH progression.

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Abstract 130: Hypercholesterolemia Suppresses Carotid Artery Endothelial NOS3 Expression via Epigenetic Mechanisms

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.130 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Alex Sotolongo ◽

Yi-Zhou Jiang ◽

John Karanian ◽

William Pritchard ◽

Peter Davies

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Endothelial Cells ◽

Dna Methyltransferase ◽

Control Group ◽

High Cholesterol Diet ◽

Cholesterol Diet ◽

High Cholesterol ◽

High Fat

Objective: One of the first clinically detectable changes in the vasculature during atherogenesis is the accumulation of cholesterol within the vessel wall. Hypercholesterolemia is characterized by dysfunctional endothelial-dependent vessel relaxation and impaired NOS3 function. Since DNA methylation at gene promoter regions strongly suppresses gene expression, we postulated that high-fat/high-cholesterol diet suppresses endothelial NOS3 through promoter DNA methylation. Methods: Domestic male pigs were fed control diet (CD) or isocaloric high fat and high cholesterol diet (HC; 12% fat and 1.5% cholesterol) for 2, 4, 8 or 12 weeks prior to tissue collection. Furthermore, to determine the effects of risk factor withdrawal, an additional group of swine received HC for 12 weeks and then CD for 8 weeks; a control group received HC continuously for 20 weeks. Endothelial cells were harvested from common carotid aorta. In parallel in vitro studies, cultured human aortic endothelial cells (HAEC) were treated with human LDL, GW3956 (LXR agonist) and RG108 (DNA methyltransferase [DNMT] inhibitor). In cells from both sources, DNA methylation at the NOS3 promoter was measured using methylation specific pyro sequencing, and endothelial gene expression was measured using RT PCR. Results: HC diet increased plasma cholesterol level from 75 mg/dl on CD to a plateau of about 540 mg/dl within 2 weeks. Endothelial NOS3 expression was significantly reduced (71±9 % of CD) after 4 weeks of HC, a level sustained at subsequent time points. Withdrawal of HC for 8 weeks did not recover NOS3 expression. After 12-week HC, the NOS3 promoter was hypermethylated. Withdrawal of HC did not reverse NOS3 promoter methylation. In vitro treatment of HAEC with human LDL (200 mg/dl total cholesterol) or GW3956 (5μM) suppressed NOS3 mRNA to 50% and 30% respectively, suggesting that LXR/RXR is involved in suppression of NOS3. Nitric oxide production was consistently suppressed by GW3959. Both could be reversed through inhibition of DNMTs by RG108. Conclusions: DNA methylation and LXR/RXR pathway can mediate the HC-suppression of endothelial NOS3. The study identifies novel pharmaceutical targets in treating endothelial dysfunction. Crosstalk between these pathways is under investigation.

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Cholic acid supplementation accelerates the progression of nonalcoholic fatty liver disease to the procarcinogenic state in mice fed a high-fat and high-cholesterol diet

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2021.108869 ◽

2021 ◽

pp. 108869

Author(s):

Hee Jeong Chun ◽

Yeon Joo Shim ◽

Young Hye Kwon

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Cholic Acid ◽

Fatty Liver Disease ◽

High Cholesterol Diet ◽

Cholesterol Diet ◽

High Cholesterol ◽

High Fat ◽

Nonalcoholic Fatty Liver

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Endothelial Function in Coronary Arterioles from Pigs with Early-stage Coronary Disease Induced by High-fat, High-cholesterol Diet: Effect of Exercise.

Cardiopulmonary Physical Therapy Journal ◽

10.1097/01823246-200516020-00009 ◽

2005 ◽

Vol 16 (2) ◽

pp. 33

Author(s):

Anne Swisher

Keyword(s):

Endothelial Function ◽

Coronary Disease ◽

Early Stage ◽

High Cholesterol Diet ◽

Cholesterol Diet ◽

High Cholesterol ◽

High Fat ◽

Coronary Arterioles

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Mangosteen Pericarp Inhibits Nuclear Factor ?B (NF-?B) Activation and Reduces Expression of ICAM-1 in High Cholesterol Diet Rat

Indonesian Journal of Cardiology ◽

10.30701/ijc.v34i1.302 ◽

2013 ◽

pp. 23-32

Author(s):

H Hendarto ◽

Mohammad Saifur Rohman ◽

Djanggan Sargowo

Keyword(s):

Crude Extract ◽

High Fat Diet ◽

Inhibitory Effect ◽

High Cholesterol Diet ◽

Cholesterol Diet ◽

High Cholesterol ◽

High Fat ◽

Factor B ◽

Underlying Risk Factor ◽

Underlying Risk

Background: Atherosclerosis is widely viewed as an inflammatory disease with hypercholesterolemia being a dominant underlying risk factor. This study aimed to determine the effect of mangosteen pericarp in inhibition of NF-?B activation and ICAM-1 expression in rat fed with high cholesterol.Methods and Results: Various doses of crude extract mangosteen pericarp were administered to the high fat diet wistar rats and the activity of NF-?B measured by immunohistochemistry to assess nuclear NF-?B expression and the ICAM-1 expression. The high fat diet resulted significant increased serum LDL levels. Increased nuclear NF- ?B activation and ICAM-1 expression were also observed in high fat diet rats in concurrence with increased serum LDL. The inhibitory effect on NF- ?B activity and ICAM-1 expression was observed when 400 mg of mangosteen pericarp crude extract was administered and even showed a higher inhibitory effect in 800 mg of mangosteen pericap treated rats. The 800 mg extract treatment resulted in decreased ICAM-1 expression similar to those of non high fat rats.Conclusion: The administration of 800 mg mangosteen pericarp crude extract significantly inhibited NF-?B activation and reversed the expression of ICAM -1 to the normal level in high cholesterol diet rats.

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Analysis Of Risk Factors Oxidative Stress In Obesity Women

Journal of Health ◽

10.30590/vol6-no1-p51-57 ◽

2019 ◽

Vol 6 (1) ◽

pp. 51-57 ◽

Cited By ~ 1

Author(s):

Alpha Olivia Hidayati ◽

Ernawati Hardani

Keyword(s):

Oxidative Stress ◽

Physical Activity ◽

Risk Factors ◽

At Risk ◽

Fat Intake ◽

Obese Women ◽

High Cholesterol ◽

High Fat ◽

Low Hdl ◽

Fiber Consumption

Obesity is a condition of imbalance in the number of calories entered by the number of calories where the excess is heaped up as body fat. Obesity followed by an increase in fat metabolism will cause Reactive Oxygen Species (ROS) production to increase. This condition causes oxidative stress. Indicators of oxidative stress can be observed from plasma levels of Malondialdehyde (MDA). This study aims to determine the risk factors for oxidative stress in obese women. The results of this study indicate that high fat intake (> 60 g / day) is at risk of increasing MDA-P levels twice. Low fiber consumption (<30 gr / day) gives the risk of an increase in MDA-P levels of 2.09 times. Poor physical activity is a risk factor for MDA-P increase of 1.15 times. High cholesterol (> 200mg / l) and LDL (> 130 mg / l) and low HDL (≤45mg / dl) levels are at risk of increasing MDA-P levels by 1.02 times (cholesterol), 1.13 (LDL) ) and 1.12 (HDL). Based on this study it can be concluded that high fat intake, low fiber intake, low physical activity, high cholesterol and HDL levels and low HDL levels are risk factors for oxidative stress.

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