Deleterious impact of elaidic fatty acid on ABCA1-mediated cholesterol efflux from mouse and human macrophages

• Published in: Biochimica et biophysica acta Vol. 1821; no. 2; pp. 303 - 312
• Main Authors: Fournier, Natalie, Attia, Nesrine, Rousseau-Ralliard, Delphine, Vedie, Benoît, Destaillats, Frédéric, Grynberg, Alain, Paul, Jean-Louis
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-02-2012; Elsevier
• Subjects: adenosine triphosphate; Adenosine Triphosphate - metabolism; adenosinetriphosphatase; Animals; atherogenesis; ATP Binding Cassette Transporter 1; ATP binding cassette transporter A1; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Biological Transport - drug effects; CD36 Antigens - metabolism; Cell Membrane - drug effects; Cell Membrane - metabolism; cholesterol; Cholesterol - metabolism; Cholesterol efflux; Diffusion - drug effects; Elaidic acid; Food and Nutrition; Gene Expression Regulation - drug effects; Human monocyte-derived macrophages; Humans; J774 mouse macrophages; Life Sciences; macrophages; Macrophages - drug effects; Macrophages - metabolism; membrane fluidity; messenger RNA; Mice; Monocytes - cytology; Oleic Acid - pharmacology; Oleic Acids - pharmacology; Other; palmitic acid; Phospholipids - metabolism; plasma membrane; protein content; RNA, Messenger - genetics; RNA, Messenger - metabolism; trans fatty acids; vaccenic acid; ABCA1; Human monocyte-derived macrophages; apo; CE; trans fatty acids; Elaidic acid; J774 mouse macrophages; ATP binding cassette transporter A1; TFA; HMDM; PL; FC; LXR/RXR; ABCG1; CHD; Cholesterol efflux; atp binding cassette transporter a1; j774 mouse macrophages; cholesterol efflux; elaidic acid; human monocyte derived macrophages
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2011.10.005

Consumption of
trans fatty acids (TFA) increase cardiovascular risk more than do saturated FA, but the mechanisms explaining their atherogenicity are still unclear. We investigated the impact of membrane incorporation of TFA on cholesterol efflux by exposing J774 mouse macrophages or human monocyte-derived macrophages (HMDM) to media enriched or not (standard medium) with industrially produced elaidic (
trans-9 18:1) acid, naturally produced vaccenic (
trans-11 18:1) acid (34
h, 70
μM) or palmitic acid. In J774 macrophages, elaidic and palmitic acid, but not vaccenic acid, reduced ABCA1-mediated efflux by ~
23% without affecting aqueous diffusion, SR-BI or ABCG1-mediated pathways, and this effect was maintained in cholesterol-loaded cells. The impact of elaidic acid on the ABCA1 pathway was weaker in cholesterol-normal HMDM, but elaidic acid induced a strong reduction of ABCA1-mediated efflux in cholesterol-loaded cells (−
36%). In J774 cells, the FA supplies had no impact on cellular free cholesterol or cholesteryl ester masses, the abundance of ABCA1 mRNA or the total and plasma membrane ABCA1 protein content. Conversely, TFA or palmitic acid incorporation induced strong modifications of the membrane FA composition with a decrease in the ratio of (
cis-monounsaturated FA
+
polyunsaturated FA):(saturated FA
+
TFA), with elaidic and vaccenic acids representing each 20% and 13% of the total FA composition, respectively. Moreover, we demonstrated that cellular ATP was required for the effect of elaidic acid, suggesting that it contributes to atherogenesis by impairing ABCA1-mediated cholesterol efflux in macrophages, likely by decreasing the membrane fluidity, which could thereby reduce ATPase activity and the function of the transporter.
► We studied the impact of membrane
trans fatty acids incorporation on cholesterol efflux from mouse and human macrophages. ► The industrially produced
trans elaidic acid specifically reduced ABCA1 cholesterol efflux pathway. ► The naturally produced
trans vaccenic acid had no impact on cholesterol efflux. ► In both cellular models, these deleterious effects were observed in cholesterol-normal or cholesterol-loaded macrophages. ► Elaidic acid may contribute to atherogenesis by impairing the ABCA1 cholesterol efflux pathway in macrophages.