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. 2010 Sep;51(9):2686-94.
doi: 10.1194/jlr.M007906. Epub 2010 Jun 3.

Differential effects of conjugated linoleic acid isomers on macrophage glycerophospholipid metabolism

Josef Ecker  1 , Gerhard Liebisch, Max Scherer, Gerd Schmitz
Affiliations

Differential effects of conjugated linoleic acid isomers on macrophage glycerophospholipid metabolism

Josef Ecker et al. J Lipid Res. 2010 Sep.

Abstract

Conjugated linoleic acids (CLA) are dietary fatty acids. Whereas cis-9,trans-11-(c9,t11)-CLA can be found in meat and dairy products, trans-9,trans-11-(t9,t11)-CLA is a constituent of vegetable oils. Previous studies showed that these two isomers activate different nuclear receptors and, thus, expression of genes related to lipid metabolism. Here we show that these CLA isomers are differentially elongated and desaturated in primary monocyte-derived macrophages isolated from healthy volunteers by using gas chromatography-mass spectrometry (GC-MS). We further demonstrate that c9,t11-CLA incorporates in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species and activates de novo glycerophospholipid synthesis by quantitative electrospray ionization-tandem mass spectrometry (ESI-MS/MS). c9,t11-CLA leads to strong shifts of the species profiles to PC 18:2/18:2 and PE 18:2/18:2, which are due to de novo synthesis and fatty acid remodeling. In contrast, t9,t11-CLA is preferentially bound to neutral lipids, including triglycerides and cholesterol esters. Taken together our results show that c9,t11-CLA and t9,t11-CLA have differential effects on PC and PE metabolism. Moreover, these data demonstrate that the structure of fatty acids not only determines their incorporation into lipid classes but also modulates the kinetics of lipid metabolism, particularly PC synthesis.

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Figures

Fig. 1.
Fig. 1.
c9,t11-CLA, but not t9,t11-CLA induces a shift to PC 36:4 and PE 36:4. A: PC species profile for untreated cells and cells treated with 10 µM CLA or linoleic acid for 4 h and quantified by ESI-MS/MS (PC 36:4 upon c9,t11-CLA treatment: P < 0.001). B: PE species profile for untreated cells and cells treated with 10 µM CLA or linoleic acid for 4 h and quantified by ESI-MS/MS (PE 36:4 upon c9,t11-CLA treatment: P < 0.001). C: PS species profile for untreated cells and cells treated with 10 µM CLA or linoleic acid for 4 h and quantified by ESI-MS/MS. Values are mean ± SD of one representative experiment from three, each performed in triplicate. CLA, conjugated linoleic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine.
Fig. 2.
Fig. 2.
PC 36:4 and PE 36:4 are primarily composed of FA 18:2. A: EPI spectrum of PC 36:4 of cells treated with 10 µM c9,t11-CLA for 4 h and analyzed by EPI spectra in negative ion mode. The product ions indicate a majority of PC 18:2/18:2 and a minor contribution of PC 16:0/20:4 to PC 36:4. B: EPI spectrum of PE 36:4 of cells treated with 10 µM c9,t11-CLA for 4 h and analyzed by EPI spectra in negative ion mode. The precursor ion of m/z 738 comprises, in addition to PE 18:2/18:2 and PE 16:0/20:4, fragment ions of chloride adduct ions of PC 30:1 and the +1 isotope peak of SM 34:1. CLA, conjugated linoleic acid; EPI, enhanced product ion; PC, phosphatidylcholine; PE, phosphatidylethanolamine; SM, sphingomyelin.
Fig. 3.
Fig. 3.
c9,t11-CLA increases de novo PC and PE synthesis via the Kennedy pathway and induces a shift toward newly synthesized PC 36:4 and PE 36:4. A: D9-PC synthesis in untreated cells and cells treated with 10 µM CLA or linoleic acid for 4 h and quantified by ESI-MS/MS. B: D4-PE synthesis in untreated cells and cells treated with 10 µM CLA or linoleic acid for 4 h and quantified by ESI-MS/MS. C: D9-PC species profile of untreated cells and cells treated with 10 µM CLA or linoleic acid for 4 h and quantified by ESI-MS/MS. D: D4-PE species profile of untreated cells and cells treated with 10 µM CLA or linoleic acid for 4 h and quantified by ESI-MS/MS. Values are mean ± SD of one representative experiment from three, each performed in triplicate (*P < 0.01). CLA, conjugated linoleic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine.
Fig. 4.
Fig. 4.
Fatty acid composition of phospholipids (PC, PE) and neutral lipids (TG, CE), and cellular free fatty acids. A: FA composition of PC for untreated cells and cells treated with 10 µM CLA or linoleic acid for 4 h, separated by TLC, methylated to generate FAMEs, and analyzed by GC-MS. B: FA composition of PE for untreated cells and cells treated with 10 µM CLA or linoleic acid for 4 h, separated by TLC, methylated to generate FAMEs, and analyzed by GC-MS. C: FA composition of TGs for untreated cells and cells treated with 10 µM CLA or linoleic acid for 4 h, separated by TLC, methylated to generate FAMEs, and analyzed by GC-MS. D: CE species profile of untreated cells and cells treated with 10 µM CLA or linoleic acid for 4 h and analyzed by ESI-MS/MS. E: FFA in untreated cells and cells treated with 10 µM CLA or linoleic acid for 4 h, separated by TLC, methylated to generate FAMEs, and analyzed by GC-MS. Values are mean ± SD of one representative experiment from three, each performed in triplicate. CLA, conjugated linoleic acid; FA, fatty acid; FFA, free fatty acid; FAME, FA methyl ester; PC, phosphatidylcholine; PE, phosphatidylethanolamine.
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