THE ROLE OF BOTANICAL OILS ENRICHED IN FADS2-DERIVED N-3 VS. N-6 POLYUNSATURATED FATTY ACIDS IN PREVENTION OF ATHEROSCLEROSIS

Abstract

Background: Dietary polyunsaturated fatty acids (PUFAs) reduce atherosclerosis in animal models and humans relative to dietary saturated and monounsaturated fatty acids. Although some of the atheroprotection of dietary PUFAs is due to plasma lipid lowering, in vivo conversion of 18 carbon PUFAs through the rate-limiting fatty acid desaturase-2 (FADS2, delta-6 desaturase) step of fatty acid desaturation and elongation results in 18 and ≥ 20 carbon PUFAs that are substrates for pro-inflammatory and anti-inflammatory eicosanoid production, which affect atherosclerosis progression and inflammation. We previously showed that an atherogenic diet containing echium oil (EO), which is relatively enriched in stearidonic acid (18:4 n-3), the immediate product of FADS2-mediated desaturation of 18:3 n-3, effectively enriches plasma and tissue lipids in the anti-inflammatory PUFA 20:5 n-3 and was as atheroprotective as dietary fish oil (FO) compared to palm oil (PO), which is enriched in saturated and monounsaturated fatty acids. However, whether a similar strategy of dietary enrichment in FADS-2 n-6 products would lead to atheroprotective is unknown. To address this gap in knowledge, we tested the hypothesis that dietary borage oil (BO), enriched in the FADS-2 product 18:3 n-6, would not be as atheroprotective as EO, due to in vivo conversion to 20:4 n-6, a pro-inflammatory eicosanoid precursor. We also investigated the role an anti-inflammatory protein G-protein coupled receptor 120(GPR120) that is activated by PUFAs in atheroprotection and hypothesized that dietary n-3 PUFAs would lead to greater activation of GPR120 and less inflammation than n-6 PUFAs.