scholarly journals Global DNA methylation in rats´ liver is not affected by hypercholesterolemic diet

2020 ◽  
pp. 347-352
Author(s):  
L. Jurcikova-Novotna ◽  
L. Mrazova ◽  
K. Micova ◽  
D. Friedecky ◽  
J.A. Hubacek ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Plasma Cholesterol ◽  
Methylation Status ◽  
Dietary Factors ◽  
Rat Strains ◽  
Total Liver ◽  
Cholesterol Levels ◽  
Hypercholesterolemic Diet ◽  
Wistar Kyoto ◽  
Atherosclerosis Risk Factors

Increased plasma cholesterol levels are listed between the major atherosclerosis risk factors. The final plasma cholesterol levels result from the interplay between the genetic and environmental (diet, physical activity) factors. Little is known, how dietary factors influence epigenetics. We have analyzed, if an over-generation feeding of rat with cholesterol influences total liver-DNA methylation, and if total liver-DNA methylation differ between the different rat strains (Prague hereditary hypercholesterolemic rats, Prague hereditary hypertriglyceridemic rats and Wistar Kyoto rats). The animals were feed with high fat (additional 5 % over normal capacity) high cholesterol (2 %) diet for 14 days. DNA methylation in the liver tissue in different generations was analyzed using the liquid chromatography coupled with tandem mass spectrometry. We have not observed any significant changes in total liver-DNA methylation over the 9 generations of animals feed by fat/cholesterol enriched diet. Additionally, there were no differences in DNA methylation between different rat strains. In animal model, the dietary changes (hypercholesterolemic diet) not significantly influence the total DNA methylation status within the liver.

DIETARY FACTORS AFFECTING THE LEVEL OF PLASMA CHOLESTEROL IN HUMANS: THE ROLE OF FAT

1956 ◽  
Vol 34 (3) ◽  
pp. 441-455 ◽  
Author(s):  
J. M. R. Beveridge ◽  
W. F. Connell ◽  
G. A. Mayer
Keyword(s):  
Corn Oil ◽  
Plasma Cholesterol ◽  
Initial Period ◽  
Dietary Factors ◽  
Chicken Fat ◽  
Animal Fats ◽  
Percentage Decrease ◽  
Cholesterol Levels ◽  
The Individual ◽  
Average Individual

Three dietary experiments have been performed in which 36, 37, and 49 male medical students and staff members participated as experimental subjects. In each study, everyone consumed the same homogeneous formula diet for eight days at which time they were divided into five groups. One group was maintained on the original diet for a further eight days and the others were given diets varying in respect of the level and nature of the fat moiety. Protein supplied 16.9% of total calories in all experimental rations. In the first experiment, 37 subjects ingested a diet providing 58.5% of calories as corn oil. During the initial period the average of the individual percentage decreases in plasma cholesterol was 32.0 (P = < 0.01). Those continuing on corn oil displayed a further insignificant decrease. The others, receiving diets high in beef dripping, chicken fat, lard, and butter showed average individual percentage increases of 11.7 (P = > 0.05), 12.7 (P = > 0.05), 15.4 (P = < 0.01), and 28.8 (P = < 0.01), respectively. In the second experiment, 49 subjects consumed a fat-free diet for eight days. The average individual percentage decrease in plasma cholesterol was 22.2 (P = < 0.01). Those continuing on the fat-free diet showed little further change. Those ingesting 20 and 60% of calories as corn oil showed further percentage decreases of 6.9 (P = > 0.05) and 15.2 (P = < 0.01), respectively. By contrast, those receiving diets providing 20 and 60%, of calories as butterfat showed respectively percentage increases of 6.6 (P = > 0.05) and 21.7 (P = < 0.01). In the third experiment, 36 subjects ingested for eight days a diet in which butterfat provided 60% of calories. The plasma cholesterol level remained essentially constant, and did not change significantly in those continuing on this diet for a further eight days. The composition of the fat moiety in the remaining groups in terms of per cent calories derived from butter-fat and corn oil respectively was: 45: 15; 30: 30; 15: 45; and 0: 60. The averages of the individual percentage decreases in plasma cholesterol values were, respectively, 3.9, 15.9, 27.1, and 32.0. Except for the lowest of these values all the changes are highly significant (P = < 0.01). In addition to other conclusions that may be drawn from this work, these studies reveal that (1) there is a factor (or are factors) in certain animal fats that acts to elevate plasma cholesterol levels, and (2) there is a factor (or are factors) in corn oil that acts to depress plasma cholesterol levels.

scholarly journals Nutritional Factors Modulating Alu Methylation in an Italian Sample from The Mark-Age Study Including Offspring of Healthy Nonagenarians

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2986
Author(s):  
Robertina Giacconi ◽  
Marco Malavolta ◽  
Alexander Bürkle ◽  
María Moreno-Villanueva ◽  
Claudio Franceschi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Preliminary Investigation ◽  
Methylation Status ◽  
Dietary Factors ◽  
Elderly Subjects ◽  
Nutritional Factors ◽  
Age Related ◽  
Potential Marker ◽  
Plasma Copper ◽  
Risk Of Disease

Alu hypomethylation promotes genomic instability and is associated with aging and age-related diseases. Dietary factors affect global DNA methylation, leading to changes in genomic stability and gene expression with an impact on longevity and the risk of disease. This preliminary study aims to investigate the relationship between nutritional factors, such as circulating trace elements, lipids and antioxidants, and Alu methylation in elderly subjects and offspring of healthy nonagenarians. Alu DNA methylation was analyzed in sixty RASIG (randomly recruited age-stratified individuals from the general population) and thirty-two GO (GeHA offspring) enrolled in Italy in the framework of the MARK-AGE project. Factor analysis revealed a different clustering between Alu CpG1 and the other CpG sites. RASIG over 65 years showed lower Alu CpG1 methylation than those of GO subjects in the same age class. Moreover, Alu CpG1 methylation was associated with fruit and whole-grain bread consumption, LDL2-Cholesterol and plasma copper. The preserved Alu methylation status in GO, suggests Alu epigenetic changes as a potential marker of aging. Our preliminary investigation shows that Alu methylation may be affected by food rich in fibers and antioxidants, or circulating LDL subfractions and plasma copper.

scholarly journals Novel RNAi-Based Therapies for Atherosclerosis

2021 ◽  
Vol 23 (8) ◽  
Author(s):  
Anna-Kaisa Ruotsalainen ◽  
Petri Mäkinen ◽  
Seppo Ylä-Herttuala
Keyword(s):  
Plasma Cholesterol ◽  
Common Factor ◽  
New Drugs ◽  
Blood Cholesterol ◽  
Advanced Treatment ◽  
Cell Debris ◽  
Cholesterol Levels ◽  
Atherosclerosis Risk ◽  
Artery Disease ◽  
Atherosclerosis Risk Factors

Abstract Purpose of Review Atherosclerosis, defined by inflammation and accumulation of cholesterol, extracellular matrix, and cell debris into the arteries is a common factor behind cardiovascular diseases (CVD), such as coronary artery disease, peripheral artery disease, and stroke. In this review, we discuss and describe novel RNA interference (RNAi)-based therapies in clinical trials and on the market. Recent Findings The first RNAi-based therapies have entered clinical use for the control of atherosclerosis risk factors, i.e., blood cholesterol levels. The most advanced treatment is silencing of proprotein convertase subtilisin/kexin type 9 (PCSK9) with a drug called inclisiran, which has been approved for the treatment of hypercholesterolemia in late 2020, and results in a robust decrease in plasma cholesterol levels. Summary As the new RNAi therapies for atherosclerosis are now entering markets, the usefulness of these therapies will be further evaluated in larger patient cohorts. Thus, it remains to be seen how fast, effectively and eminently these new drugs consolidate their niche within the cardiovascular disease drug palette.

scholarly journals High Cholesterol Diet Exacerbates Blood-Brain Barrier Disruption in LDLr–/– Mice: Impact on Cognitive Function

2020 ◽  
Vol 78 (1) ◽  
pp. 97-115
Author(s):  
Jade de Oliveira ◽  
Daiane F. Engel ◽  
Gabriela C. de Paula ◽  
Danúbia B. dos Santos ◽  
Jadna B. Lopes ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Familial Hypercholesterolemia ◽  
Blood Brain Barrier ◽  
Plasma Cholesterol ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
Wild Type ◽  
High Cholesterol ◽  
Cholesterol Levels ◽  
Hypercholesterolemic Diet

Background: Evidence has revealed an association between familial hypercholesterolemia and cognitive impairment. In this regard, a connection between cognitive deficits and hippocampal blood-brain barrier (BBB) breakdown was found in low-density lipoprotein receptor knockout mice (LDLr–/–), a mouse model of familial hypercholesterolemia. Objective: Herein we investigated the impact of a hypercholesterolemic diet on cognition and BBB function in C57BL/6 wild-type and LDLr–/–mice. Methods: Animals were fed with normal or high cholesterol diets for 30 days. Thus, wild-type and LDLr–/–mice were submitted to memory paradigms. Additionally, BBB integrity was evaluated in the mice’s prefrontal cortices and hippocampi. Results: A tenfold elevation in plasma cholesterol levels of LDLr–/–mice was observed after a hypercholesterolemic diet, while in wild-type mice, the hypercholesterolemic diet exposure increased plasma cholesterol levels only moderately and did not induce cognitive impairment. LDLr–/–mice presented memory impairment regardless of the diet. We observed BBB disruption as an increased permeability to sodium fluorescein in the prefrontal cortices and hippocampi and a decrease on hippocampal claudin-5 and occludin mRNA levels in both wild-type and LDLr–/–mice treated with a hypercholesterolemic diet. The LDLr–/–mice fed with a regular diet already presented BBB dysfunction. The BBB-increased leakage in the hippocampi of LDLr–/–mice was related to high microvessel content and intense astrogliosis, which did not occur in the control mice. Conclusion: Therefore, LDLr–/–mice seem to be more susceptible to cognitive impairments and BBB damage induced by exposure to a high cholesterol diet. Finally, BBB disruption appears to be a relevant event in hypercholesterolemia-induced brain alterations.

DIETARY FACTORS AFFECTING THE LEVEL OF PLASMA CHOLESTEROL IN HUMANS: THE ROLE OF FAT

1956 ◽  
Vol 34 (1) ◽  
pp. 441-455 ◽  
Author(s):  
J. M. R. Beveridge ◽  
W. F. Connell ◽  
G. A. Mayer
Keyword(s):  
Corn Oil ◽  
Plasma Cholesterol ◽  
Initial Period ◽  
Dietary Factors ◽  
Chicken Fat ◽  
Animal Fats ◽  
Percentage Decrease ◽  
Cholesterol Levels ◽  
The Individual ◽  
Average Individual

Three dietary experiments have been performed in which 36, 37, and 49 male medical students and staff members participated as experimental subjects. In each study, everyone consumed the same homogeneous formula diet for eight days at which time they were divided into five groups. One group was maintained on the original diet for a further eight days and the others were given diets varying in respect of the level and nature of the fat moiety. Protein supplied 16.9% of total calories in all experimental rations. In the first experiment, 37 subjects ingested a diet providing 58.5% of calories as corn oil. During the initial period the average of the individual percentage decreases in plasma cholesterol was 32.0 (P = < 0.01). Those continuing on corn oil displayed a further insignificant decrease. The others, receiving diets high in beef dripping, chicken fat, lard, and butter showed average individual percentage increases of 11.7 (P = > 0.05), 12.7 (P = > 0.05), 15.4 (P = < 0.01), and 28.8 (P = < 0.01), respectively. In the second experiment, 49 subjects consumed a fat-free diet for eight days. The average individual percentage decrease in plasma cholesterol was 22.2 (P = < 0.01). Those continuing on the fat-free diet showed little further change. Those ingesting 20 and 60% of calories as corn oil showed further percentage decreases of 6.9 (P = > 0.05) and 15.2 (P = < 0.01), respectively. By contrast, those receiving diets providing 20 and 60%, of calories as butterfat showed respectively percentage increases of 6.6 (P = > 0.05) and 21.7 (P = < 0.01). In the third experiment, 36 subjects ingested for eight days a diet in which butterfat provided 60% of calories. The plasma cholesterol level remained essentially constant, and did not change significantly in those continuing on this diet for a further eight days. The composition of the fat moiety in the remaining groups in terms of per cent calories derived from butter-fat and corn oil respectively was: 45: 15; 30: 30; 15: 45; and 0: 60. The averages of the individual percentage decreases in plasma cholesterol values were, respectively, 3.9, 15.9, 27.1, and 32.0. Except for the lowest of these values all the changes are highly significant (P = < 0.01). In addition to other conclusions that may be drawn from this work, these studies reveal that (1) there is a factor (or are factors) in certain animal fats that acts to elevate plasma cholesterol levels, and (2) there is a factor (or are factors) in corn oil that acts to depress plasma cholesterol levels.

DNA Methylation Status of Mash2 in Lungs of Somatic Cell Cloning Bovines*

2010 ◽  
Vol 37 (9) ◽  
pp. 960-966 ◽  
Author(s):  
Jie CHEN ◽  
Dong-Jie LI ◽  
Cui ZHANG ◽  
Ning LI ◽  
Shi-Jie LI
Keyword(s):  
Dna Methylation ◽  
Somatic Cell ◽  
Methylation Status ◽  
Cell Cloning

scholarly journals Epigenetic Changes During Mechanically Induced Osteogenic Lineage Commitment

2015 ◽  
Vol 137 (2) ◽  
Author(s):  
Julia C. Chen ◽  
Mardonn Chua ◽  
Raymond B. Bellon ◽  
Christopher R. Jacobs
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Methylation Status ◽  
Lineage Commitment ◽  
Fluid Shear ◽  
Osteogenic Lineage ◽  
Osteogenic Markers ◽  
Heterochromatin Structure

Osteogenic lineage commitment is often evaluated by analyzing gene expression. However, many genes are transiently expressed during differentiation. The availability of genes for expression is influenced by epigenetic state, which affects the heterochromatin structure. DNA methylation, a form of epigenetic regulation, is stable and heritable. Therefore, analyzing methylation status may be less temporally dependent and more informative for evaluating lineage commitment. Here we analyzed the effect of mechanical stimulation on osteogenic differentiation by applying fluid shear stress for 24 hr to osteocytes and then applying the osteocyte-conditioned medium (CM) to progenitor cells. We analyzed gene expression and changes in DNA methylation after 24 hr of exposure to the CM using quantitative real-time polymerase chain reaction and bisulfite sequencing. With fluid shear stress stimulation, methylation decreased for both adipogenic and osteogenic markers, which typically increases availability of genes for expression. After only 24 hr of exposure to CM, we also observed increases in expression of later osteogenic markers that are typically observed to increase after seven days or more with biochemical induction. However, we observed a decrease or no change in early osteogenic markers and decreases in adipogenic gene expression. Treatment of a demethylating agent produced an increase in all genes. The results indicate that fluid shear stress stimulation rapidly promotes the availability of genes for expression, but also specifically increases gene expression of later osteogenic markers.

Plasma cholesterol levels in free-ranging macaques compared with captive macaques and humans

Primates ◽  
2000 ◽  
Vol 41 (3) ◽  
pp. 299-309 ◽  
Author(s):  
Akiko Takenaka ◽  
Yuko Matsumoto ◽  
Aika Nagaya ◽  
Kunio Watanabe ◽  
Shunji Goto ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Cholesterol Levels ◽  
Free Ranging

scholarly journals DNA methylation differs extensively between strains of the same geographical origin and changes with age in Daphnia magna

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jack Hearn ◽  
Fiona Plenderleith ◽  
Tom J. Little
Keyword(s):  
Dna Methylation ◽  
Caloric Restriction ◽  
Daphnia Magna ◽  
Single Gene ◽  
Methylation Status ◽  
Strain Differences ◽  
Life History Trait ◽  
Food Level ◽  
Epigenetic Clock ◽  
Age Related

Abstract Background Patterns of methylation influence lifespan, but methylation and lifespan may also depend on diet, or differ between genotypes. Prior to this study, interactions between diet and genotype have not been explored together to determine their influence on methylation. The invertebrate Daphnia magna is an excellent choice for testing the epigenetic response to the environment: parthenogenetic offspring are identical to their siblings (making for powerful genetic comparisons), they are relatively short lived and have well-characterised inter-strain life-history trait differences. We performed a survival analysis in response to caloric restriction and then undertook a 47-replicate experiment testing the DNA methylation response to ageing and caloric restriction of two strains of D. magna. Results Methylated cytosines (CpGs) were most prevalent in exons two to five of gene bodies. One strain exhibited a significantly increased lifespan in response to caloric restriction, but there was no effect of food-level CpG methylation status. Inter-strain differences dominated the methylation experiment with over 15,000 differently methylated CpGs. One gene, Me31b, was hypermethylated extensively in one strain and is a key regulator of embryonic expression. Sixty-one CpGs were differentially methylated between young and old individuals, including multiple CpGs within the histone H3 gene, which were hypermethylated in old individuals. Across all age-related CpGs, we identified a set that are highly correlated with chronological age. Conclusions Methylated cytosines are concentrated in early exons of gene sequences indicative of a directed, non-random, process despite the low overall DNA methylation percentage in this species. We identify no effect of caloric restriction on DNA methylation, contrary to our previous results, and established impacts of caloric restriction on phenotype and gene expression. We propose our approach here is more robust in invertebrates given genome-wide CpG distributions. For both strain and ageing, a single gene emerges as differentially methylated that for each factor could have widespread phenotypic effects. Our data showed the potential for an epigenetic clock at a subset of age positions, which is exciting but requires confirmation.

Sign in / Sign up

Export Citation Format

Share Document