Ascorbic acid and α-tocopherol down-regulate apolipoprotein A-I gene expression in HepG2 and Caco-2 cell lines

Mooradian, Arshag D.; Haas, Michael J.; Wadud, Khuram

doi:10.1016/j.metabol.2005.08.008

Cited by 16 publications

(6 citation statements)

References 39 publications

(41 reference statements)

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“…The interdependence of these vitamins and lipids (as demonstrated in Table 3) suggests that the interactions described in this study may be either just reflective of the strong correlation between vitamins and lipids or biological relevance. In support of the latter interpretation, micronutrients such as vitamin A and E have previously been implicated in affecting the gene expression of import lipid-metabolizing genes [15,16,27,28,33]. For example, Mooradian et al demonstrated that high concentrations of vitamin E were associated with significant decreases in apoA-I expression (which is sensitive to the oxidative state of the cell) in hepatic HepG2 cells by reducing apoA-I promoter activity [27].…”

Section: Discussionmentioning

confidence: 93%

Serum vitamins A and E as modifiers of lipid trait genetics in the National Health and Nutrition Examination Surveys as part of the Population Architecture using Genomics and Epidemiology (PAGE) study

et al. 2012

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Objective Lipid-associated genetic variants discovered through genome-wide association studies (GWAS) do not account for the majority of heritability estimated for these traits. Epidemiological studies have long indicated that certain environmental factors are capable of shaping lipid distributions. However, environmental modifiers of known genotype-phenotype associations are just recently emerging in the literature. Research Methods & Procedures We genotyped GWAS-identified variants in samples collected for the National Health and Nutrition Examination Surveys (NHANES). NHANES is a cross-sectional survey of Americans representing non-Hispanic whites (n=2,435), non-Hispanic blacks (n=1,407), and Mexican Americans (n=1,734). Along with lipid levels, NHANES contains an abundance of environmental variables, including serum vitamin A and E levels, both of which are antioxidants that may play a role in lipid metabolism. Gene-environment interactions were modeled between either vitamin A or ln(vitamin E) and 23 GWAS-identified lipid-associated variants for HDL-C, LDL-C, and ln(TG) levels. Results After adjusting for age, sex, and marginal effects, three SNPxvitamin A and six SNPxvitamin E interactions were identified at a significance threshold of p<2.2×10−3. The most significant interaction was APOB rs693xvitamin E (p=8.9×10−7) for LDL-C levels among Mexican Americans; this same interaction was significant in non-Hispanic whites (p=2.67×10−4) but not non-Hispanic Blacks (p=0.11). The nine significant interaction models individually explained 0.35–1.28% of the variation in one of the lipid traits. Conclusions Our results suggest that the vitamins A and E impact GWAS-identified associations for lipid traits; however, these significant interactions account for only a fraction of the overall variability observed for HDL-C, LDL-C, and TG levels in the general population.

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Section: Discussionmentioning

confidence: 93%

Serum vitamins A and E as modifiers of lipid trait genetics in the National Health and Nutrition Examination Surveys as part of the Population Architecture using Genomics and Epidemiology (PAGE) study

et al. 2012

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“…Large doses of antioxidant vitamins may partially blunt HDLc induction by simvastatin and niacin combination therapy (90). The apo A‐I promoter is sensitive to the oxidative state of the cell and some antioxidants, at high concentrations, can suppress apo A‐I promoter activity (91). Apo A‐I gene transcription is also affected by large doses of vitamin D (92) and vitamin A (93).…”

Section: Effect Of Dietary Compositionmentioning

confidence: 99%

Obesity‐related Changes in High‐density Lipoprotein Metabolism

Mooradian

Haas

Wehmeier

et al. 2008

Obesity

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Obesity is associated with a 3‐or‐more‐fold increase in the risk of fatal and nonfatal myocardial infarction (1,2,3,4,5,6). The American Heart Association has reclassified obesity as a major, modifiable risk factor for coronary heart disease (7). The increased prevalence of premature coronary heart disease in obesity is attributed to multiple factors (8,9,10). A principal contributor to this serious morbidity is the alterations in plasma lipid and lipoprotein levels. The dyslipidemia of obesity is commonly manifested as high plasma triglyceride levels, low high‐density lipoprotein cholesterol (HDLc), and normal low‐density lipoprotein cholesterol (LDLc) with preponderance of small dense LDL particles (7,8,9,10). However, there is a considerable heterogeneity of plasma lipid profile in overweight and obese people. The precise cause of this heterogeneity is not entirely clear but has been partly attributed to the degree of visceral adiposity and insulin resistance. The emergence of glucose intolerance or a genetic predisposition to familial combined hyperlipidemia will further modify the plasma lipid phenotype in obese people (11,12,13,14,15).

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“…Large doses of antioxidant vitamins may partially blunt the HDL-C induction by simvastatin and niacin combination therapy [34]. The Apo A-I promoter is sensitive to the oxidative state of the cell and, at high concentrations, some antioxidants can suppress its activity [35]. Apparently, however, high-dose vitamin C supplementation (1 g/day) does not have consistent effects on plasma lipids or lipoprotein levels [23].…”

Section: Nutrition and Hdlmentioning

confidence: 99%

High-Density Lipoprotein: Therapeutic Target, 1 Year On

Sirtori

2007

Future Lipidology

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Ascorbic acid and α-tocopherol down-regulate apolipoprotein A-I gene expression in HepG2 and Caco-2 cell lines

Cited by 16 publications

References 39 publications

Serum vitamins A and E as modifiers of lipid trait genetics in the National Health and Nutrition Examination Surveys as part of the Population Architecture using Genomics and Epidemiology (PAGE) study

Serum vitamins A and E as modifiers of lipid trait genetics in the National Health and Nutrition Examination Surveys as part of the Population Architecture using Genomics and Epidemiology (PAGE) study

Obesity‐related Changes in High‐density Lipoprotein Metabolism

High-Density Lipoprotein: Therapeutic Target, 1 Year On

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