Deuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia
| Autor: | Ginger L. Milne, Rensen Pcn., Mikhail S. Shchepinov, Isabel M. Mol, Geerte Hoeke, Erik D. Pollock, van der Ploeg Lht., Claudia Monaco, Berbée Jfp., D Lütjohann |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Apolipoprotein E medicine.medical_specialty Time Factors Mice Knockout ApoE Lipid peroxidation Hypercholesterolemia Aortic Diseases Apolipoprotein E3 Dinoprost Weight Gain Antioxidants 03 medical and health sciences chemistry.chemical_compound Internal medicine medicine Animals Cholesterol metabolism Genetic Predisposition to Disease Aorta Adiposity chemistry.chemical_classification F2-Isoprostanes Chemistry Cholesterol Anticholesteremic Agents food and beverages Metabolism Atherosclerosis Plaque Atherosclerotic eye diseases Sterol Cholesterol Ester Transfer Proteins Disease Models Animal Phenotype 030104 developmental biology Endocrinology Biochemistry Fatty Acids Unsaturated Lean body mass Intestinal cholesterol absorption Female lipids (amino acids peptides and proteins) Polyunsaturated fatty acids Cardiology and Cardiovascular Medicine Biomarkers Polyunsaturated fatty acid |
| Zdroj: | Atherosclerosis, 264, 100-107 |
| Popis: | Background and aim Oxidative modification of lipoproteins is a crucial step in atherosclerosis development. Isotopic-reinforced polyunsaturated fatty acids (D-PUFAs) are more resistant to reactive oxygen species-initiated chain reaction of lipid peroxidation than regular hydrogenated (H-)PUFAs. We aimed to investigate the effect of D-PUFA treatment on lipid peroxidation, hypercholesterolemia and atherosclerosis development. Methods Transgenic APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism, were pre-treated with D-PUFAs or control H-PUFAs-containing diet (1.2%, w/w) for 4 weeks. Thereafter, mice were fed a Western-type diet (containing 0.15% cholesterol, w/w) for another 12 weeks, while continuing the D-/H-PUFA treatment. Results D-PUFA treatment markedly decreased hepatic and plasma F2-isoprostanes (approx. -80%) and prostaglandin F2α (approx. -40%) as compared to H-PUFA treatment. Moreover, D-PUFAs reduced body weight gain during the study (-54%) by decreasing body fat mass gain (-87%) without altering lean mass. D-PUFAs consistently reduced plasma total cholesterol levels (approx. -25%), as reflected in reduced plasma non-HDL-cholesterol (- 28%). Additional analyses of hepatic cholesterol metabolism indicated that D-PUFAs reduced the hepatic cholesterol content (-21%). Sterol markers of intestinal cholesterol absorption and cholesterol breakdown were decreased. Markers of cholesterol synthesis were increased. Finally, D-PUFAs reduced atherosclerotic lesion area formation throughout the aortic root of the heart (-26%). Conclusions D-PUFAs reduce body weight gain, improve cholesterol handling and reduce atherosclerosis development by reducing lipid peroxidation and plasma cholesterol levels. DPUFAs therefore represent a promising new strategy to broadly reduce rates of lipid peroxidation, and combat hypercholesterolemia and cardiovascular diseases. |
| Databáze: | OpenAIRE |
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