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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #226438
Title: Reduction in Dietary Omega-6 Polyunsaturated Fatty Acids: Eicosapentaenoic Acid plus Docosahexaenoic Acid Ratio Minimizes Atherosclerotic Lesion Formation and Inflammatory Response in the LDL Receptor Null Mouse

Author
item WANG, SHU - HNRCA AT TUFTS UNIVERSITY
item WU, DAYONG - HNRCA AT TUFTS UNIVERSITY
item MATTHAN, NIRUPA - HNRCA AT TUFTS UNIVERSITY
item LAMON-FAVA, STEFANIA - HNRCA AT TUFTS UNIVERSITY
item LECKER, JAIME - HNRCA AT TUFTS UNIVERSITY
item Lichtenstein, Alice

Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/10/2008
Publication Date: 5/1/2009
Citation: Wang, S., Wu, D., Matthan, N.R., Lamon-Fava, S., Lecker, J.L., Lichtenstein, A.H. 2009. Reduction in Dietary Omega-6 Polyunsaturated Fatty Acids: Eicosapentaenoic Acid plus Docosahexaenoic Acid Ratio Minimizes Atherosclerotic Lesion Formation and Inflammatory Response in the LDL Receptor Null Mouse. Atherosclerosis. 204(1):147-155.

Interpretive Summary: Dietary very long chain omega -3 polyunsaturated fatty acids (PUFA), found primarily in fish, have been associated with reduced heart disease risk, the mechanisms of which have yet to be fully elucidated. A mouse that has a genetic defect similar to that found in some humans with premature heart disease, the LDL receptor null mice (LDLr-/-) were used to assess the effect of different ratios of common plant derived PUFA (omega-6 PUFA) to fish based PUFA (omega-3:EPA+DHA) on aortic lesion formation and inflammatory response. Mice were fed high saturated fat diets (HSF), to promote aortic lesion formation, without EPA and DHA (HSF omega-6), or with omega-6:EPA+DHA at ratios of 20:1 (HSF R=20:1), 4:1 (HSF R=4:1), and 1:1 (HSF R=1:1) for 32 weeks. Mice fed the lowest omega-6:EPA+DHA ratio diet had lower non-HDL cholesterol concentrations (bad cholesterol) and the inflammatory factor interleukin-6 (IL-6) compared to mice fed the HSF omega-6 diet. Aortic and elicited peritoneal macrophage (M-phi''total cholesterol content were both lower in HSF R=1:1 compared to HSF omega-6 fed mice. Another factor associated with aortic lesions, MCP-1, mRNA levels and secretion levels were lower in elicited peritoneal M phi isolated from mice fed the higher compared to lower omega-6:EPA+DHA ratio diets. These data suggest that lower omega-6:EPA+DHA ratio diets lowered some measures of inflammation and M phi cholesterol accumulation, which was associated with less aortic lesion formation in LDLr-/- mice.

Technical Abstract: Dietary very long chain omega-3 polyunsaturated fatty acids (PUFA) have been associated with reduced CVD risk. LDL receptor null mice (LDLr-/-) were used to assess different dietary ratios of omega-6 PUFA to eicosapentaenoic acid plus docosahexaenoic acid (omega-6:EPA+DHA) on atherogenesis and inflammatory response. Mice were fed high saturated fat diets without EPA and DHA (HSF omega-6), or with omega-6:EPA+DHA at ratios of 20:1 (HSF R=20:1), 4:1 (HSF R=4:1) and 1:1 (HSF R=1:1) for 32 weeks. Mice fed lowest omega-6:EPA+DHA ratio diet had lower non-HDL cholesterol (25%, P<0.05) and interleukin-6 (IL-6) (44%, P<0.05) concentrations compared to mice fed HSF omega-6 diet. Aortic and elicited peritoneal macrophage (M phi total cholesterol were 24% (P=0.07) and 25% (P<0.05) lower, respectively, in HSF R=1:1 compared to HSF omega-6 fed mice. MCP-1 mRNA levels and secretion were 37% (P<0.05) and 38% (P<0.05) lower, respectively, in peritoneal M phi from HSF R=1:1 compared to HSF omega-6 fed mice. mRNA and protein ATP-binding cassette A1 and mRNA TNF-alpha levels were significantly lower in peritoneal M phi isolated from HSF R=1:1 fed mice. These data suggest that LDLr-/- mice fed lower omega-6:EPA+DHA ratio diets had lower inflammatory response and M phi cholesterol accumulation, which in turn was associated with less aortic lesion formation.