Deleterious impact of elaidic [i]trans[/i] fatty acid on ABCA1-mediated cholesterol efflux from mouse and human and human macrophages - Archive ouverte HAL Access content directly
Conference Papers Year : 2012

Deleterious impact of elaidic [i]trans[/i] fatty acid on ABCA1-mediated cholesterol efflux from mouse and human and human macrophages

Abstract

Consumption of trans fatty acids (TFA) increases cardiovascular risk more than do saturated FA but the mechanisms explaining their atherogenicity are still unclear. We investigated the impact of membrane TFA incorporation on the 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 or palmitic acid (34 h, 70 µM). In J774 macrophages, elaidic and palmitic acids, 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 ABCA1 pathway was weaker on cholesterol-normal HMDM, but elaidic acid induced a strong reduction of ABCA1-efflux in cholesterol- loaded cells (-36%). In J774 cells, the FA supplementations had no impact on cellular free cholesterol or cholesteryl esters masses, the abundance of ABCA1 mRNA or the total and plasma membrane ABCA1 protein contents. Conversely, TFA or palmitic acid incorporation induced strong modifications of the membrane FA composition with a decrease in the ratio (cis-monounsatured 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, suggesting that it contributes to atherogenesis by impairing the ABCA1 cholesterol efflux in macrophages, likely by decreasing the membrane fluidity, which could thereby reduce ATPase activity and the function of the transporter.
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Dates and versions

hal-01189896 , version 1 (01-09-2015)

Identifiers

  • HAL Id : hal-01189896 , version 1
  • PRODINRA : 254990

Cite

Natalie Fournier, N. Attia, Delphine Rousseau-Ralliard, B. Vedie, F. Destaillats, et al.. Deleterious impact of elaidic [i]trans[/i] fatty acid on ABCA1-mediated cholesterol efflux from mouse and human and human macrophages. 80. EAS Congress, European Atherosclerosis Society. SWE., May 2012, Milan, Italy. ⟨hal-01189896⟩
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