Abstract 121: Role of Leukocyte Gpr120 in Atherosclerosis Development in Polyunsaturated Fatty Acid Diet Induced Atheroprotection in LDLrKO Mice
Introduction Diets enriched in polyunsaturated n-3 and n-6 fatty acids (PUFAs) are atheroprotective. FO, which is enriched in n-3 PUFAs, reduces plasma lipids and has anti-inflammatory effects. Recent studies have shown that GPR120 is the physiological n-3 PUFA receptor and its ligation by n-3 PUFAs blunts pro-inflammatory signaling pathways. However, the role of GRP120 in atherogenesis is unknown.
Hypothesis We hypothesized that leukocyte GPR120 contributes to the atheroprotective effects of n-3, but not n-6, PUFUs by ligation of GRP120, resulting in decreased leukocyte inflammation.
Methods Female LDLr-/- mice were transplanted with bone marrow from male wild type or GPR120 knockout mice. After recovery from transplantation, recipient LDLr-/- mice were fed atherogenic diets containing 0.2% cholesterol and enriched in saturated/monounsaturated fat (palm oil, PO), n-6 PUFA (borage, BO), a botanical n-3 PUFA (echium oil, EO) or FO for 16 weeks. Periodic blood samples were taken for lipid and lipoprotein measurements and aortas were harvested after 16 weeks of diet feeding to quantify atherosclerosis.
Results Compared to the PO group, mice fed BO, EO and FO had significantly lower plasma total and very low density lipoprotein (VLDL) cholesterol concentrations. EO and FO groups also had lower plasma triglyceride concentrations compare to PO and BO fed mice. Compared to the PO group, mice fed BO and EO had significantly reduced aortic CE, comparable to the FO group. However, lack of leukocyte GPR120 did not significantly affect plasma lipids or atherosclerosis severity within any diet group.
Conclusion Atherogenic diets enriched in n-6 and n-3 PUFAs derived from botanical oils (BO and EO) were as atheroprotective as FO compared to a diet containing saturated/monounsaturated fat (PO). Furthermore, lack of leukocyte GPR120 had minimal effect on plasma lipid/lipoprotein profile and atherosclerosis, suggesting that n-3 as well as n-6 PUFA associated atheroprotection is primarily due to reduction of VLDL-cholesterol in LDLr-/- mice.
- © 2013 by American Heart Association, Inc.