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Incremental replacement of saturated fats by n-3 fatty acids in high-fat, high-cholesterol diets reduces elevated plasma lipid levels and arterial lipoprotein lipase, macrophages and atherosclerosis in LDLR-/- mice.
Atherosclerosis. 2014 Jun; 234(2):401-9.A

Abstract

OBJECTIVE

Effects of progressive substitution of dietary n-3 fatty acids (FA) for saturated FA (SAT) on modulating risk factors for atherosclerosis have not been fully defined. Our previous reports demonstrate that SAT increased, but n-3 FA decreased, arterial lipoprotein lipase (LpL) levels and arterial LDL-cholesterol deposition early in atherogenesis. We now questioned whether incremental increases in dietary n-3 FA can counteract SAT-induced pro-atherogenic effects in atherosclerosis-prone LDL-receptor knockout (LDLR-/-) mice and have identified contributing mechanisms.

METHODS AND RESULTS

Mice were fed chow or high-fat diets enriched in SAT, n-3, or a combination of both SAT and n-3 in ratios of 3:1 (S:n-3 3:1) or 1:1 (S:n-3 1:1). Each diet resulted in the expected changes in fatty acid composition in blood and aorta for each feeding group. SAT-fed mice became hyperlipidemic. By contrast, n-3 inclusion decreased plasma lipid levels, especially cholesterol. Arterial LpL and macrophage levels were increased over 2-fold in SAT-fed mice but these were decreased with incremental replacement with n-3 FA. n-3 FA partial inclusion markedly decreased expression of pro-inflammatory markers (CD68, IL-6, and VCAM-1) in aorta. SAT diets accelerated advanced atherosclerotic lesion development, whereas all n-3 FA-containing diets markedly slowed atherosclerotic progression.

CONCLUSION

Mechanisms whereby dietary n-3 FA may improve adverse cardiovascular effects of high-SAT, high-fat diets include improving plasma lipid profiles, increasing amounts of n-3 FA in plasma and the arterial wall. Even low levels of replacement of SAT by n-3 FA effectively reduce arterial lipid deposition by decreasing aortic LpL, macrophages and pro-inflammatory markers.

Authors+Show Affiliations

Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA.Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Campus Norte Hospital Roberto del Río, University of Chile, Santiago, Chile.Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA.Campus Norte Hospital Roberto del Río, University of Chile, Santiago, Chile.Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: rjd20@columbia.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24747115

Citation

Chang, Chuchun L., et al. "Incremental Replacement of Saturated Fats By N-3 Fatty Acids in High-fat, High-cholesterol Diets Reduces Elevated Plasma Lipid Levels and Arterial Lipoprotein Lipase, Macrophages and Atherosclerosis in LDLR-/- Mice." Atherosclerosis, vol. 234, no. 2, 2014, pp. 401-9.
Chang CL, Torrejon C, Jung UJ, et al. Incremental replacement of saturated fats by n-3 fatty acids in high-fat, high-cholesterol diets reduces elevated plasma lipid levels and arterial lipoprotein lipase, macrophages and atherosclerosis in LDLR-/- mice. Atherosclerosis. 2014;234(2):401-9.
Chang, C. L., Torrejon, C., Jung, U. J., Graf, K., & Deckelbaum, R. J. (2014). Incremental replacement of saturated fats by n-3 fatty acids in high-fat, high-cholesterol diets reduces elevated plasma lipid levels and arterial lipoprotein lipase, macrophages and atherosclerosis in LDLR-/- mice. Atherosclerosis, 234(2), 401-9. https://doi.org/10.1016/j.atherosclerosis.2014.03.022
Chang CL, et al. Incremental Replacement of Saturated Fats By N-3 Fatty Acids in High-fat, High-cholesterol Diets Reduces Elevated Plasma Lipid Levels and Arterial Lipoprotein Lipase, Macrophages and Atherosclerosis in LDLR-/- Mice. Atherosclerosis. 2014;234(2):401-9. PubMed PMID: 24747115.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Incremental replacement of saturated fats by n-3 fatty acids in high-fat, high-cholesterol diets reduces elevated plasma lipid levels and arterial lipoprotein lipase, macrophages and atherosclerosis in LDLR-/- mice. AU - Chang,Chuchun L, AU - Torrejon,Claudia, AU - Jung,Un Ju, AU - Graf,Kristin, AU - Deckelbaum,Richard J, Y1 - 2014/04/03/ PY - 2014/01/06/received PY - 2014/02/28/revised PY - 2014/03/18/accepted PY - 2014/4/22/entrez PY - 2014/4/22/pubmed PY - 2015/1/13/medline KW - Atherosclerosis KW - Inflammation KW - LDLR−/− KW - Lipoprotein lipase KW - n−3 fatty acids SP - 401 EP - 9 JF - Atherosclerosis JO - Atherosclerosis VL - 234 IS - 2 N2 - OBJECTIVE: Effects of progressive substitution of dietary n-3 fatty acids (FA) for saturated FA (SAT) on modulating risk factors for atherosclerosis have not been fully defined. Our previous reports demonstrate that SAT increased, but n-3 FA decreased, arterial lipoprotein lipase (LpL) levels and arterial LDL-cholesterol deposition early in atherogenesis. We now questioned whether incremental increases in dietary n-3 FA can counteract SAT-induced pro-atherogenic effects in atherosclerosis-prone LDL-receptor knockout (LDLR-/-) mice and have identified contributing mechanisms. METHODS AND RESULTS: Mice were fed chow or high-fat diets enriched in SAT, n-3, or a combination of both SAT and n-3 in ratios of 3:1 (S:n-3 3:1) or 1:1 (S:n-3 1:1). Each diet resulted in the expected changes in fatty acid composition in blood and aorta for each feeding group. SAT-fed mice became hyperlipidemic. By contrast, n-3 inclusion decreased plasma lipid levels, especially cholesterol. Arterial LpL and macrophage levels were increased over 2-fold in SAT-fed mice but these were decreased with incremental replacement with n-3 FA. n-3 FA partial inclusion markedly decreased expression of pro-inflammatory markers (CD68, IL-6, and VCAM-1) in aorta. SAT diets accelerated advanced atherosclerotic lesion development, whereas all n-3 FA-containing diets markedly slowed atherosclerotic progression. CONCLUSION: Mechanisms whereby dietary n-3 FA may improve adverse cardiovascular effects of high-SAT, high-fat diets include improving plasma lipid profiles, increasing amounts of n-3 FA in plasma and the arterial wall. Even low levels of replacement of SAT by n-3 FA effectively reduce arterial lipid deposition by decreasing aortic LpL, macrophages and pro-inflammatory markers. SN - 1879-1484 UR - https://www.unboundmedicine.com/medline/citation/24747115/Incremental_replacement_of_saturated_fats_by_n_3_fatty_acids_in_high_fat_high_cholesterol_diets_reduces_elevated_plasma_lipid_levels_and_arterial_lipoprotein_lipase_macrophages_and_atherosclerosis_in_LDLR_/__mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(14)00171-3 DB - PRIME DP - Unbound Medicine ER -