Deuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia.
<h4>Background and aim</h4> <p>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 regul...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2017
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| _version_ | 1797070103571857408 |
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| author | Berbée, JFP Mol, IM Milne, GL Pollock, E Hoeke, G Lütjohann, D Monaco, C Rensen, PCN van der Ploeg, LHT Shchepinov, MS |
| author_facet | Berbée, JFP Mol, IM Milne, GL Pollock, E Hoeke, G Lütjohann, D Monaco, C Rensen, PCN van der Ploeg, LHT Shchepinov, MS |
| author_sort | Berbée, JFP |
| collection | OXFORD |
| description | <h4>Background and aim</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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%).</p> <h4>Conclusions</h4> <p>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.</p> |
| first_indexed | 2024-03-06T22:34:16Z |
| format | Journal article |
| id | oxford-uuid:59589471-a4c7-4bf1-bbc8-506ee11f8ce4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:34:16Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:59589471-a4c7-4bf1-bbc8-506ee11f8ce42022-03-26T17:09:10ZDeuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:59589471-a4c7-4bf1-bbc8-506ee11f8ce4EnglishSymplectic Elements at OxfordElsevier2017Berbée, JFPMol, IMMilne, GLPollock, EHoeke, GLütjohann, DMonaco, CRensen, PCNvan der Ploeg, LHTShchepinov, MS <h4>Background and aim</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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%).</p> <h4>Conclusions</h4> <p>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.</p> |
| spellingShingle | Berbée, JFP Mol, IM Milne, GL Pollock, E Hoeke, G Lütjohann, D Monaco, C Rensen, PCN van der Ploeg, LHT Shchepinov, MS Deuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia. |
| title | Deuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia. |
| title_full | Deuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia. |
| title_fullStr | Deuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia. |
| title_full_unstemmed | Deuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia. |
| title_short | Deuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia. |
| title_sort | deuterium reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia |
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