Linoleic acid suppresses cholesterol efflux and ATP‐binding cassette transporters in murine bone marrow‐derived macrophages

Abstract

BackgroundIndividuals with diabetes are at increased cardiovascular disease (CVD) risk, possibly associated with elevated plasma free fatty acids (FA). Evidence suggests that elevated unsaturated (U)FA suppress macrophage cholesterol efflux, a mechanism implicated in CVD risk. Murine bone marrow‐derived macrophages (BMDM) were used to explore the relationship between elevated UFA and cholesterol efflux mediated by ATP‐binding cassette transporters (ABCA1 and ABCG1) and transcription factors liver‐x‐receptor‐alpha (LXR‐α) and sterol receptor element binding protein (SREBP)‐1.Methods/ResultsBMDM were stimulated with 100 uM linoleic acid (LA) or palmitic acid (PA) for 16 hrs, and exposed to 25 ug/mL oxidized low density lipoprotein (oxLDL) for 24 hr. LA and PA each suppressed ABCA1 mRNA (60% and 30%, respectively) and ABCG1 mRNA (54% and 29%, respectively) (all p<0.01). LA decreased high density lipoprotein (HDL) mediated cholesterol efflux by 53% and ABCA1 protein by 94% (both p<0.05) with no significant effect on ABCG1, LXR‐α or SREBP‐1 protein.ConclusionThese results suggest that elevated LA attenuates macrophage HDL‐mediated cholesterol efflux through alterations in ABCA1 mRNA and protein but not by regulating LXR‐α or SREBP‐1 expression. This mechanism may contribute to diabetes‐associated CVD.NHLIBI‐T32‐HL069772, USDA 58–1950‐0–0014