Deuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia

作者：Berbee Jimmy F P; Mol Isabel M; Milne Ginger L; Pollock Erik; Hoeke Geerte; Luetjohann Dieter; Monaco Claudia; Rensen Patrick C N; van der Ploeg Lex H T; Shchepinov Mikhail S

来源：Atherosclerosis, 2017, 264: 100-107.

DOI：10.1016/j.atherosclerosis.2017.06.916

• Polyunsaturated fatty acids
• Lipid peroxidation
• Hypercholesterolemia
• Cholesterol metabolism
• Atherosclerosis

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 F-2 alpha (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.

• 出版日期2017-9