Abstract
Trans fatty acid (TFA) consumption causes adverse changes in plasma lipids and lipoprotein profile, which leads to increased incidence of atherosclerosis. Macrophage cholesterol efflux, an atheroprotective process, is mediated by ATP binding cassette transporter A1 (ABCA1). ABCA1 is highly regulated by transcription factors Liver X receptor‐α (LXRα) and Retinoic X Receptor‐α (RXRα). Our studies are focusing on the mechanism by which individual trans fatty acid molecular species regulate ABCA1‐mediated macrophage cholesterol efflux and macrophage cholesterol efflux. Our results show that trans fatty acid species differentially regulate ABCA1 protein expression in mouse macrophage J774. The most abundant trans fatty acid elaidic acid (9t‐18:1) protects ABCA1 protein degradation, whereas oleic acid (9c‐18:1) induce ABCA1 protein degradation. Elaidic acid upregulates LXRα/RXRα activity and sterol regulatory element (SRE)‐driven luciferase activity, which suggest that elaidic acid may increase activities of sterol regulatory element binding proteins (SREBPs) family. These results demonstrated that trans fatty acids regulate ABCA1‐mediated cholesterol efflux and cholesterol homeostasis in a distinctive way compared to cis fatty acids.This research was supported by NIH grants HL074214 and HL098907 (DAF)
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