Deuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia. (September 2017)

• Record Type: Journal Article
• Authors: Berbée, Jimmy F.P.; Mol, Isabel M.; Milne, Ginger L.; Pollock, Erik; Hoeke, Geerte; Lütjohann, Dieter; Monaco, Claudia; Rensen, Patrick C.N.; van der Ploeg, Lex H.T.; Shchepinov, Mikhail S.
• Is Part Of: Atherosclerosis. Volume 264(2017)
• Page Start: 100
• Page End: 107
• Publication Date: 2017-09
• Subjects: Polyunsaturated fatty acids -- Lipid peroxidation -- Hypercholesterolemia -- Cholesterol metabolism -- Atherosclerosis; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2017.06.916
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: 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 at investigating 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 F2 α (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. D-PUFAs, therefore, represent a promising new strategy to broadly reduce rates of lipid peroxidation, and combat hypercholesterolemia and cardiovascular diseases. Highlights: D-PUFAs decrease lipid peroxidation products in hyperlipidemic mice. D-PUFAs reduce body weight and body fat mass gain. D-PUFAs lower plasma cholesterol levels and improve cholesterol handling. D-PUFAs reduce atherosclerotic lesion formation.